Cerebrospinal Fluid Analysis

If the CSF has been collected under sterile conditions, microbiologic studies can now be
performed. Stains, cultures, and immunoglobulin titers may be obtained; the last are of special
importance with diseases in which peripheral manifestations fade while central nervous system
(CNS) symptoms persist (eg, syphilis and Lyme disease).[1, 2, 3]
Different institutions have different protocols for the studies performed on the various CSF
tubes. The classic approach is to send the 4 CSF tubes for the following studies:

Tube 1 - Cell count and differential

Tube 2 - Glucose and protein levels

Tube 3 - Gram stain, culture and sensitivity (C&S)

Tube 4 - Cell count and differential

At some institutions, only 3 tubes are sent for analysis, and tube 4 is reserved for special studies
when indicated. In this approach, the following studies are done:

Tube 1 - Protein and glucose levels

Tube 2 - Gram stain, C&S

Tube 3 - Cell count and differential

When indicated, viral titers or cultures, Venereal Disease Research Laboratory (VDRL) tests,
Cryptococcus antigen assays, India ink stains, angiotensin-converting enzyme (ACE) levels, or
other studies are ordered. Additional tests may be warranted, depending on the clinical situation.
All specimens should be taken to the laboratory promptly to prevent hemolysis and specimen
misplacement.
Separate specimens should be sent for microscopic study and for centrifugation. The latter must
be done promptly because red blood cells (RBCs) hemolyze within a few hours. The lymphocyte
count in normal CSF may be as high as 5/L.

Cytologic assessment
A larger-than-usual number of white blood cells (WBCs) suggests an infection or, more rarely,
leukemic infiltration. Although bacterial infections are traditionally associated with a
preponderance of polymorphonuclear leukocytes (PMNs), many cases of viral meningitis and
encephalitis also show a high percentage of PMNs in the acute phase of the illness (when most

lumbar punctures are done). In addition, inflammation from any source (eg, CNS vasculitis) can
raise the WBC count.
A traumatic tap, of course, introduces WBCs and RBCs into the CSF (see Complications). An
approximation of 1 WBC for every 1000 RBCs can be made, though a repeat tap may be
preferable. Although no normal value for RBCs in the CSF is known, an occasional RBC may be
incident to the tap itself.
Multiple lumbar puncture examinations may be required in testing for leptomeningeal
malignancies. At least 3 negative cytologic evaluations (ie, 3 separate samplings) are required to
rule out leptomeningeal malignancy (eg, leptomeningeal carcinomatosis).

Protein assessment
Assessment of CSF protein level, though nonspecific, can be a clue to otherwise unsuspected
neurologic disease. The high protein levels in demyelinating polyneuropathies, or postinfectious
states, can be informative. A traumatic tap can introduce protein into the CSF. An approximation
of 1 mg of protein for every 750 RBCs may be used, but a repeat tap is preferable.

Glucose assessment
The CSF glucose level normally approximates 60% of the peripheral blood glucose level at the
time of the tap. A simultaneous measurement of blood glucose (especially if the CSF glucose
level is likely to be low) is recommended.
A low CSF glucose level is usually associated with bacterial infection (probably due to
enzymatic inhibition rather than to actual bacterial consumption of the glucose). This finding is
also seen in tumor infiltration and may be one of the hallmarks of meningeal carcinomatosis,
even with negative cytologic findings. A high CSF glucose level has no specific diagnostic
significance and is most often spillover from an elevated blood glucose level.

Xanthochromia
The best way of distinguishing RBCs related to intracranial bleeding is to examine the
centrifuged supernatant CSF for xanthochromia (yellow color). Although xanthochromia can be
confirmed visually, it is more accurately identified and quantified in the laboratory.
Although xanthochromia can be produced by spillover from a very high serum bilirubin level (>
15 mg/dL), patients with severe hyperbilirubinemia (eg, from jaundice or known liver disease).
usually have been identified before lumbar puncture. With this exception, xanthochromia in a
freshly spun specimen is evidence of preexistent blood in the subarachnoid space. However, it
should be remembered that an extremely high CSF protein level, as seen in lumbar punctures
below a complete spinal block, also renders the fluid xanthochromic, though without RBCs.
Xanthochromia can persist for as long as several weeks after a subarachnoid hemorrhage (SAH).
Thus, it has greater diagnostic sensitivity than computed tomography (CT) of the head without
contrast, especially if the SAH occurred more than 3-4 days before presentation. Patients with

aneurysmal leaks (eg, sentinel hemorrhages) may present days after the onset of headache, and
this increases the likelihood of a false-negative head CT scan.
In some cases, the CSF may be another color that strongly suggests a diagnosis. For example,
pseudomonal meningitis may be associated with bright-green CSF.

Cerebrospinal Fluid Analysis

This short reference guide provides generic information that may guide initial interpretation of
cerebrospinal fluid (CSF) studies but should not be used alone for determination of normal or
abnormal results. For further information, see Lumbar Puncture.
The patients specific factors (which are beyond the scope of this brief guide), as well as the
reference range variability among different laboratories, must be considered by the treating
provider when obtaining and interpreting tests.[1]
Caution is warranted in the routine clinical use of existing clinical predictive rules for bacterial
meningitis until high diagnostic performance is prospectively validated.[2]
Approximately 90% of immunocompetent patients with culture-proven meningitis have CSF
findings characteristic of acute community-acquired bacterial meningitis. Immunocompromised
patients and patients with tuberculosis meningitis may present with acellular/lowwhite blood
cell (WBC)CSF meningitis.[3, 4]

Normal results in adults

See the list below:

Appearance: Clear

Opening pressure: 10-20 cm H 2 O

WBC count: 0-5 cells/L (< 2 polymorphonucleocytes [PMN]); normal cell counts do
not rule out meningitis or any other pathology

Glucose level: >60% of serum glucose

Protein level: < 45 mg/dL

Consider additional tests: CSF culture, others depending on clinical findings

Bacterial meningitis
See the list below:

Appearance: Clear, cloudy, or purulent

Opening pressure: Elevated (>25 cm H 2 O)

WBC count: >100 cells/L (>90% PMN); partially treated cases may have as low as 1
WBC/L

Glucose level: Low (< 40% of serum glucose)

Protein level: Elevated (>50 mg/dL)

Consider additional tests: CSF Gram stain and cultures, blood cultures, CSF bacterial antigens,
CSF polymerase chain reaction (PCR), others depending on clinical findings

Aseptic (viral) meningitis

See the list below:

Appearance: Clear

Opening pressure: Normal or elevated

WBC count: 10-1000 cells/L (lymph but PMN early)

Glucose level: >60% serum glucose (may be low in HSV infection)

Protein level: Elevated (>50 mg/dL)

Consider additional tests: CSF Gram stain and cultures, blood cultures, CSF bacterial antigens,
CSF PCR (eg, herpes simplex virus [HSV], varicella-zoster virus [VZV]), others depending on
clinical findings

Fungal meningitis
See the list below:

Appearance: Clear or cloudy

Opening pressure: Elevated

WBC count: 10-500 cells/L

Glucose level: Low

Protein level: Elevated

Consider additional tests: CSF Gram stain and cultures, blood cultures, CSF bacterial antigens,
CSF PCR, CSF India ink, others depending on clinical findings

Tuberculosis
See the list below:

Appearance: Clear or opaque

Opening pressure: Elevated

WBC count: 50-500 cells/L (early PMN then lymph)

Glucose level: Low

Protein level: Elevated

Consider additional tests: CSF Gram stain and cultures, blood cultures, CSF bacterial antigens,
CSF PCR, CSF tuberculosis culture/stain, others depending on clinical findings

Subarachnoid hemorrhage
See the list below:

Appearance: Xanthochromia, bloody, or clear

Opening pressure: Elevated

WBC count: (1 additional WBC per 1000 RBCs is considered normal correction)

Glucose level: Normal

Protein level: Elevated

Consider additional tests: CSF Gram stain and cultures, others depending on clinical findings

Multiple sclerosis
See the list below:

Appearance: Clear

Opening pressure: Normal

WBC count: 0-20 cells/L (lymph)

Glucose level: Normal

Protein level: Mildly elevated (45-75 mg/dL)

Consider additional tests: Oligoclonal band analysis (serum and CSF), others depending on
clinical findings

Guillain Barr syndrome

See the list below:

Appearance: Clear or xanthochromia

Opening pressure: Normal or elevated

WBC count: Normal or elevated

Glucose level: Normal

Protein level: Elevated