Cerebrospinal Fluid (CSF) Analysis

Cerebrospinal fluid (CSF) analysis is a laboratory test to examine a sample of the fluid surrounding the brain and spinal cord. This fluid is a clear, watery liquid that protects the central nervous system from injury and cushions it from the surrounding bone structure. It contains a variety of substances, particularly glucose (sugar), protein, and white blood cells from the immune system. The fluid is withdrawn through a needle in a procedure called a lumbar puncture.

Functions

CSF serves four primary purposes:

      1- Buoyancy: The actual mass of the human brain is about 1400 grams; however the net weight of the brain suspended in the CSF is equivalent to a mass of 25 grams. The brain therefore exists in neutral buoyancy, which allows the brain to maintain its density without being impaired by its own weight, which would cut off blood supply and kill neurons in the lower sections without CSF.

      2- Protection: CSF protects the brain tissue from injury when jolted or hit. In certain situations such

as auto accidents or sports injuries, the CSF cannot protect the brain from forced contact with the skull case, causing hemorrhaging, brain damage, and sometimes death.

    3- Chemical stability: CSF flows throughout the inner ventricular system in the brain and is absorbed back into the bloodstream, rinsing the metabolic waste from the central nervous system through the blood-brain barrier. This allows for homeostatic regulation of the distribution of neuroendocrine factors, to which slight changes can cause problems or damage to the nervous system. For example, high glycine concentration disrupts temperature and blood pressure control, and high CSF pH causes dizziness and syncope.

    4- Prevention of brain ischemia: The prevention of brain ischemia is made by decreasing the amount of CSF in the limited space inside the skull. This decreases total intracranial pressure and facilitates blood perfusion.

Purpose

The purpose of a CSF analysis is to diagnose medical disorders that affect the central nervous system. Some of these conditions include:

1-viral and bacterial infections, such as meningitis and encephalitis.

2- tumors    or cancers of the nervous system.

3- syphilis, a sexually transmitted disease.

4- bleeding (hemorrhaging) around the brain and spinal cord.

5- multiple  sclerosis, a disease that affects the myelin coating of the nerve fibers of the brain and spinal cord.

6- Guillain-Barre syndrome, an inflammation of the nerves.

Description

Routine examination of CSF includes visual observation of color and clarity and tests for glucose, protein, lactate, lactate dehydrogenase, red blood cell count, white blood cell count with differential, syphilis serology (testing for antibodies indicative of syphilis), Gram stain, and bacterial culture. Further tests may need to be performed depending upon the results of initial tests and the presumptive diagnosis. For example, an abnormally high total protein seen in a patient suspected of having a demyelinating disease such as multiple sclerosis dictates CSF protein electrophoresis and measurement of immunoglobulin levels and myelin basic protein.

GROSS EXAMINATION. Color and clarity are important diagnostic characteristics of CSF. Straw, pink, yellow, or amber pigments (xanthochromia) are abnormal and indicate the presence of bilirubin, hemoglobin, red blood cells, or increased protein. Turbidity (suspended particles) indicates an increased number of cells.

GLUCOSE. CSF glucose is normally approximately two-thirds of the fasting plasma glucose. A glucose level below 40 mg/dL is significant and occurs in bacterial and fungal meningitis and in malignancy.

PROTEIN. Total protein levels in CSF are normally very low, and albumin makes up approximately twothirds of the total. High levels are seen in many conditions including bacterial and fungal meningitis, multiple sclerosis, tumors, subarachnoid hemorrhage, and traumatic tap.

LACTATE. The CSF lactate is used mainly to help differentiate bacterial and fungal meningitis, which cause increased lactate, from viral meningitis, which does not.

LACTATE DEHYDROGENASE. This enzyme is elevated in bacterial and fungal meningitis, malignancy, and subarachnoid hemorrhage.

WHITE BLOOD CELL (WBC) COUNT. The number of white blood cells in CSF is very low, usually necessitating a manual WBC count. An increase in WBCs may occur in many conditions including infection (viral, bacterial, fungal, and parasitic), allergy, leukemia, multiple sclerosis, hemorrhage, traumatic tap, encephalitis, and Guillain-Barre syndrome. The WBC differential helps to distinguish many of these causes. For example, viral infection is usually associated with an increase in lymphocytes, while bacterial and fungal infections are associated with an increase in polymorphonuclear leukocytes (neutrophils). The differential may also reveal eosinophils associated with allergy and ventricular shunts; macrophages with ingested bacteria (indicating meningitis), RBCs (indicating hemorrhage), or lipids (indicating possible cerebral infarction); blasts (immature cells) that indicate leukemia; and malignant cells characteristic of the tissue of origin. About 50% of metastatic cancers that infiltrate the central nervous system and about 10% of central nervous system tumors will shed cells into the CSF.

RED BLOOD CELL (RBC) COUNT. While not normally found in CSF, RBCs will appear whenever bleeding has occurred. Red cells in CSF signal subarachnoid hemorrhage, stroke, or traumatic tap.

GRAM STAIN. The Gram stain is performed on a sediment of the CSF and is positive in at least 60% of cases of bacterial meningitis. Culture is performed for both aerobic and anaerobic bacteria. In addition, other stains (e.g. the acid-fast stain for Mycobacterium tuberculosis , fungal culture, and rapid identification tests [tests for bacterial and fungal antigens]) may be performed routinely.

SYPHILIS SEROLOGY. This involves testing for antibodies that indicate neurosyphilis. The fluorescent treponemal antibody-absorption (FTA-ABS) test is often used and is positive in persons with active and treated syphilis. The test is used in conjunction with the VDRL test for nontreponemal antibodies, which is positive in most persons with active syphilis, but negative in treated cases.

Cytology Usage. Establish the presence of primary or metastatic neoplasm; diagnosis of cryptococcal meningitis, bacterial meningitis, cerebral hemorrhage, brain abscess, encephalitis (postinfection, tick borne), lead encephalopathy, medulloblastoma, neurosyphilis, sarcoidosis (meningeal); and study of CNS changes related to acquired immunodeficiency syndrome.

Factors That Affect Results

1-      The results are invalid when the specimen stands over 1 hour at room temperature.

2- Previous radiation, intrathecal therapy, myelogram, or pneumoencephalogram may cause cytologic changes that produce false results.

3- Microbiologic studies should be performed on tube 3 or higher to lessen the chance of skin contamination.

4- At least 5 mL is necessary to detect fungal and mycobacterial infections.

5- If CNS infection is strongly suspected but initial cell counts are normal, the test should be repeated a few hours later to detect rising white cell counts.

6- Store CSF for culture in a bacteriologic incubator when not tested promptly.

7- A portion of the sample should be frozen at -20 degrees C when viral meningitis is suspected.

Normal results

• Gross appearance: Normal CSF is clear and colorless.
•  CSF opening pressure: 50-175 mm H ₂ O.
• Specific gravity: 1.006-1.009.
• Glucose: 40-80 mg/dL.
• Total protein: 15-45 mg/dL.
• LD: 1/10 of serum level.
• Lactate: less than 35 mg/dL.
• Leukocytes (white blood cells): 0-5/microL (adults and children);    up to 30/microL (newborns).
• Differential: 60-80% lymphocytes; up to 30% monocytes and macrophages; other cells 2% or less. Monocytes and macrophages are somewhat higher in neonates.
• Gram stain: negative.
• Culture: sterile.
• Syphilis serology: negative.

• Red blood cell count: Normally, there are no red blood cells in the CSF unless the needle passes through a blood vessel on route to the CSF.