Cerebrospinal Fluid Studies
OVERVIEW OF CEREBROSPINAL FLUID (CSF)
Description, Formation, and Composition of CSF
Cerebrospinal fluid (CSF) is a clear, colorless fluid formed within the cavities (i.e., ventricles) of the brain. The choroid plexus produces about 70% of the CSF by ultrafiltration and secretion. The ependymal lining of the ventricles and cerebral subarachnoid space produce the remainder of the CSF total volume. About 500 mL of CSF fluid is formed per day, although only 90 to 150 mL is present in the system at any one time. Reabsorption of CSF occurs at the arachnoid villi.
CSF circulates slowly from the ventricular system into the space surrounding the brain and spinal cord and serves as a hydraulic shock absorber, diffusing external forces to the skull that might otherwise cause severe injury. The CSF also helps to regulate intracranial pressure (ICP), supply nutrients to the nervous tissues, and remove waste products. The chemical composition of CSF does not resemble an ultrafiltrate of plasma. Certain chemicals in the CSF are regulated by specific transport systems (e.g., K+, Ca2+, Mg2+), whereas other substances (e.g., glucose, urea, creatinine) diffuse freely. Proteins enter the CSF by passive diffusion at a rate dependent on the plasma-to-CSF concentration gradient. The term blood-brain barrier is used to represent the control and filtration of blood plasma components (e.g., restriction of protein diffusion from blood into brain tissue) to the CSF and then to the brain capillaries. The ratio of increased albumin in CSF to blood serum is always caused by blood-brain barrier dysfunction because albumin is found extensively in blood. A decreased CSF flow rate is due to decreased production or restriction or blockage of flow.
Most CSF constituents are present in the same or lower concentrations as in the blood plasma, except for chloride concentrations, which are usually higher (Table 5.1). Disease, however, can cause elements ordinarily restrained by the blood-brain barrier to enter the spinal fluid. Erythrocytes and leukocytes can enter the CSF from the rupture of blood vessels or from meningeal reaction to irritation. Bilirubin can be found in the spinal fluid after intracranial hemorrhage. In such cases, the arachnoid granulations and the nerve root sheaths will reabsorb the bloody fluid. Normal CSF pressure will consequently be maintained by the reabsorption of CSF in amounts equal to its production. Blockage causes an increase in the amount of CSF, resulting in hydrocephalus in infants or increased ICP in adults. Of the many factors that regulate the level of CSF pressure, venous pressure is the most important because the reabsorbed fluid ultimately drains into the venous system.
Despite the continuous production (about 0.3 mL/min) and reabsorption of CSF and the exchange of substances between the CSF and the blood plasma, considerable pooling occurs in the lumbar sac. The lumbar sac, located at L4 to L5, is the usual site used for puncture to obtain CSF specimens because damage to the nervous system is less likely to occur in this area. In infants, the spinal cord is situated more caudally than in adults (L3-L4 until 9 months of age, when the cord ascends to L1-L2); therefore, a low lumbar puncture should be made in these patients.
Explanation of Tests
CSF, obtained by lumbar-intrathecal puncture, is the main diagnostic tool for neurologic disorders. A lumbar-intrathecal puncture is done for the following reasons:
To examine the spinal fluid for diagnosis of four major disease categories:
Meningitis
Subarachnoid hemorrhage
CNS malignancy (meningeal carcinoma, tumor metastasis)
Autoimmune disease and multiple sclerosis
To determine level of CSF pressure, to document impaired CSF flow, or to lower pressure by removing volume of fluid (fluid removal should be done with caution)
TABLE 5.1 Normal CSF Values
Volume
Appearance
Pressure
Total cell count
Adult: 90-150 mL; child: 60-100 mL
Crystal clear, colorless
Adult: 90-180 mm H2O; child: 10-100 mm H2O
Essentially free cells
Adults
Newborn (0-14 d)
WBCs
Differential
0-5 cells
0-30 cells
Lymphocytes
40%-80% (0.40-0.80)
5%-35% (0.05-0.35)
Monocytes
15%-45% (0.15-0.45)
50%-90% (0.50-0.90)
Polys
0%-6% (0-0.06)
0%-8% (0-0.08)
RBCs (has limited diagnostic value)
Specific gravity
1.006-1.008
Clinical Tests
Glucose
40-70 mg/dL (2.2-3.9 mmol/L)
60-80 mg/dL (3.3-4.4 mmol/L)
Protein
Lumbar
Adults: 15-45 mg/dL (150-450 mg/L)
Neonates: 15-100 mg/dL (150-1000 mg/L)
Elderly (>60 y): 15-60 mg/dL (150-600 mg/L)
Cisternal
15-25 mg/dL (150-250 mg/L)
Ventricular
5-15 mg/dL (50-150 mg/L)
Lactic acid (lactate)
10-24 mg/dL (1.11-2.66 mmol/L)
Glutamine
5-20 mg/dL (0.34-1.37 mmol/L)
Albumin
10-35 mg/dL (1.52-5.32 mmol/L)
Urea nitrogen
6-16 mg/dL (2.14-5.71 mmol/L)
Creatinine
0.5-1.2 mg/dL (44-106 mmol/L)
Uric acid
0.5-4.5 mg/dL (29.7-268 mmol/L)
Bilirubin
0 (none)
Phosphorus
1.2-2.0 mg/dL (387-646 mmol/L)
Ammonia
10-35 mg/dL (5.87-20.5 mmol/L)
Lactate dehydrogenase (LDH) (10% of serum level)
Adult: 0-40 U/L (0-0.67 mkat/L)
Electrolytes and pH
pH
Lumbar
7.28-7.32
Cisternal
7.32-7.34
Chloride
115-130 mEq/L (mmol/L)
Sodium
135-160 mEq/L (mmol/L)
Potassium
2.6-3.0 mEq/L (mmol/L)
CO2 content
20-25 mEq/L (mmol/L)
PCO2
44-50 mm Hg (5.8-6.6 kPa)
PO2
40-44 mm Hg (5.3-5.8 kPa)
Calcium
2.0-2.8 mEq/L (mmol/L)
1.0-1.4 mEq/L (mmol/L)
Magnesium
2.4-3.0 mEq/L (mmol/L)
1.2-1.5 mEq/L (mmol/L)
Osmolality
280-300 mOsm/kg (280-300 mmol/kg)
Serology and Microbiology
VDRL
Negative
Bacteria
None present
Viruses
None present
Antibody index
>1.5 indicates chronic inflammatory process
<0.4 probably not acute inflammatory process
Be sure to include patient’s age because it is needed to evaluate borderline values.
To identify disease-related immunoglobulin patterns (IgG, IgA, and IgM referenced to albumin) in neurotuberculosis, neuroborreliosis (after a tick bite), or opportunistic infections
To introduce anesthetics, drugs, or contrast media used for radiographic studies and nuclear scans into the spinal cord
To confirm the identity of pathogens involved in acute inflammatory or chronic inflammatory disorders (e.g., multiple sclerosis and blood-brain barrier dysfunction)
To identify extent of brain infarction or stroke
To formulate antibody index (AI) of the IgG class for polyspecific immune response in the central nervous system (CNS). Examples: measles, rubella, and zoster (MRZ) antibodies to viruses in multiple sclerosis (MS); herpes simplex virus (HSV) antibodies in MS; toxoplasma antibodies in MS; and autoantibodies to double-stranded deoxyribonucleic acid (ds-DNA)
To identify brain-derived proteins, such as neuron-specific enolase present after brain trauma
See Figure 5.1 for an example of a CSF analysis report.
CLINICAL ALERTThe MRZ reaction occurs in MS, lupus erythematosus, Sjögren’s syndrome, and Wegener’s granulomatosis.
Certain observations are made each time lumbar puncture is performed:
CSF pressure is measured.
General appearance, consistency, and tendency of the CSF to clot are noted.
CSF cell count is performed to distinguish types of cells present; this must be done within 2 hours of obtaining the CSF sample.
CSF protein and glucose concentrations are determined.
Other clinical serologic and bacteriologic tests are done when the patient’s condition warrants (e.g., culture for aerobes and anaerobes or tuberculosis).
Tumor markers may be present in CSF; these tests are useful as supplements to CSF cytology analysis (Table 5.2).
 FIGURE 5.1. Cerebrospinal fluid analysis report. (From Regeniter A, Steiger JU, Scholer A, Huber PR, Siede WH: Windows to the ward: Graphically oriented report forms. Presentation of complex, interrelated laboratory data for electrophoresis/immunofixation, cerebrospinal fluid, and urinary protein profiles. Clin Chem 49:1, 41-50, 2003, Fig. 2; Reprinted with permission of AACC.) |
TABLE 5.2 Tumor Markers in CSF | ||||||||||||||||||||||||
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CLINICAL ALERT1. Blood levels for specific substances should always be measured simultaneously with CSF determinations for meaningful interpretation of results.
2. Before lumbar puncture, check eyegrounds (fundus of the eye as visualized with an ophthalmoscope) for evidence of papilledema (swelling of the optic disc generally due to an increase in intracranial pressure) because its presence may signal potential problems or complications of lumbar puncture.
3. A mass lesion should be precluded by computed tomography (CT) scan before lumbar puncture because this can lead to brainstem herniation.
4. However, if increased pressure is found while performing the lumbar puncture, it should not be necessary to stop the procedure unless neurologic signs are present.
CEREBROSPINAL FLUID TESTS
Lumbar Puncture (Spinal Tap)Procedure
1. Place the patient in a side-lying position with the head flexed onto the chest and knees drawn up to, but not compressing, the abdomen to “bow” the back. This position helps to increase the space between the lower lumbar vertebrae so that the spinal needle can be inserted more easily between
the spinal processes. However, a sitting position with the head flexed to the chest can be used. The patient is helped to relax and instructed to breathe slowly and deeply with his or her mouth open.
the spinal processes. However, a sitting position with the head flexed to the chest can be used. The patient is helped to relax and instructed to breathe slowly and deeply with his or her mouth open.
 FIGURE 5.2. Spinal tap technique. The patient lies on one side with knees flexed and back arched to separate the lumbar vertebrae. The patient is surgically draped, and an area overlying the lumbar spine is disinfected (A). The space between lumbar vertebrae L4 and L5 is palpated with sterile gloved forefinger (B), and the spinal needle is carefully directed between the spinous processes, through the infraspinous ligaments, into the spinal canal (C). |
2. Select the puncture site, usually between L4 and L5 or lower. There is a small bony landmark at the L5-S1 interspace known as the “surgeon’s delight” that helps to locate the puncture site. The site is thoroughly cleansed with an antiseptic solution, and the surrounding area is draped with sterile towels in such a way that the drapes do not obscure important landmarks (Fig. 5.2).
3. Inject a local anesthetic slowly into the dermis around the intended puncture site.
4. Insert a spinal needle with stylet into the midline between the spines of the lumbar space and slowly advance until it enters the subarachnoid space. The patient may feel the entry as a “pop” of the needle through the dura mater. Once this happens, the patient can be helped to straighten his or her legs slowly to relieve abdominal compression.
5. Remove the stylet with the needle remaining in the subarachnoid space and attach a pressure manometer to the needle to record the opening CSF pressure.
PROCEDURAL ALERT1. If the opening pressure is more than 200 mm H2O in a relaxed patient, no more than 2 mL of CSF should be withdrawn.
2. If the initial pressure is normal, Queckenstedt’s test may be done. (This test is not done if a CNS tumor is suspected.) In this test, pressure is placed on both jugular veins to occlude them temporarily and to produce an acute rise in CSF pressure. Normally, pressure rapidly returns to average levels after jugular vein occlusion is removed. Total or partial spinal fluid blockage is diagnosed if the lumbar pressure fails to rise when both jugular veins are compressed or if the pressure requires more than 20 seconds to fall after compression is released.
6. Remove a specimen consisting of up to 20 mL CSF. Take up to four samples of 2 to 3 mL each, place in separate sterile vials, and label sequentially. Tube 1 is used for chemistry and serology; tube 2 is used for microbiology studies; tube 3 is used for hematology cell counts; and tube 4 is used for special studies such as cryptococcal antigens, syphilis testing (Venereal Disease Research Laboratory [VDRL]), protein electrophoresis, and other immunologic studies. A closing pressure reading may be taken before the needle is withdrawn. In cases of increased ICP, no more than 2 mL is withdrawn because of the risk that the brainstem may shift.
7. Apply a small sterile dressing to the puncture site.
8. Label tubes correctly with the proper sequential number (1, 2, 3, or 4), the patient’s name, and the date of collection. Specimens of CSF must be immediately delivered to the laboratory, where they should be given to laboratory personnel with specific instructions regarding the testing. CSF samples should never be placed in the refrigerator because refrigeration alters the results of bacteriologic and fungal studies. Analysis should be started immediately. If viral studies are to be done, a portion of the specimen should be frozen.
9. Record procedure start and completion times, patient’s status, CSF appearance, and CSF pressure readings.
Interventions
Pretest Patient Care
1. Explain the purpose, benefits, and risks of lumbar puncture and explain tests to be performed on the CSF specimen; present a step-by-step description of the actual procedure. Emphasize the need for patient cooperation. Assess for contraindications or impediments such as arthritis. Sedation or analgesia may be used.
2. Help the patient to relax by having him or her breathe slowly and deeply. The patient must refrain from breath holding, straining, moving, and talking during the procedure.
3. Follow guidelines in Chapter 1 regarding safe, effective, informed pretest care.
Posttest Patient Care
1. Have the patient lie prone (flat or horizontal, or on the abdomen) for approximately 4 to 8 hours. Turning from side to side is permitted as long as the body is kept in a horizontal position.
2. Women may have difficulty voiding in this position. The use of a fracture bedpan may help.
3. Fluids are encouraged to help prevent or relieve headache, which is a possible result of lumbar puncture.
4. Interpret test outcomes. Assess and monitor for abnormal outcomes and complications such as paralysis (or progression of paralysis, as with spinal tumor), hematoma, meningitis, asphyxiation of infants due to tracheal obstruction from pushing the head forward, and infection. Initiate infection control precautions if test outcomes reveal an infectious process.
5. Observe for neurologic changes such as altered level of consciousness, change of pupils, change in temperature, increased blood pressure, irritability, and numbness and tingling sensations, especially in the lower extremities.
6. If headache occurs, administer analgesics as ordered and encourage a longer period of prone bed rest. If headache persists, a “blood patch” may need to be done, in which a small amount of the patient’s own blood is introduced into the spinal canal at the same level that the canal was previously entered. For reasons not totally understood, this blood patch very effectively stops spinal headaches within a very short period.
7. Check the puncture site for leakage.
8. Document the procedure completion and any problems encountered or complaints voiced by the patient.
9. Follow guidelines in Chapter 1 regarding safe, effective, informed posttest care.
CLINICAL ALERT1. Extreme caution should be used when performing lumbar puncture:
If intracranial pressure (ICP) is elevated, especially in the presence of papilledema or split cranial sutures. However, with some cases of increased ICP, such as with a coma, intracranial bleeding, or suspected meningitis, the need to establish a diagnosis is absolutely essential and outweighs the risks of the procedure.
A relative contraindication would be ICP from a suspected mass lesion. To reduce the risk for brain herniation, a less invasive procedure such as a CT scan or magnetic resonance imaging (MRI) should be done.
2. Contraindications to lumbar puncture include the following conditions:
Suspected epidural infection
Infection or severe dermatologic disease in the lumbar area, which may be introduced into the spinal canal
Severe psychiatric or neurotic problems
Chronic back pain
Anatomic malformations, scarring in puncture site areas, or previous spinal surgery at the site
3. If there is CSF leakage at the puncture site, notify the physician immediately and document findings.
4. Follow standard precautions (see Appendix A) when handling CSF specimens.
CSF PressureThe CSF pressure is directly related to pressure in the jugular and vertebral veins that connect with the intracranial dural sinuses and the spinal dura. In conditions such as congestive heart failure or obstruction of the superior vena cava, CSF pressure is increased, whereas in circulatory collapse, CSF pressure is decreased.
Pressure measurement is done to detect impairment of CSF flow or to lower the CSF pressure by removing a small volume of CSF fluid. Provided initial pressure is not elevated and there is no marked fall in the pressure as fluid is removed, 10 to 20 mL of CSF may be removed without danger to the patient. Elevation of the opening CSF pressure may be the only abnormality found in patients with cryptococcal meningitis and pseudotumor cerebri. Repeated lumbar punctures are performed for ICP elevation in cryptococcal meningitis to decrease the CSF pressure.
Reference Values
Normal
Adult: 90-180 mm H2O (or 9-18 cm H2O) in the lateral recumbent position. (This value is position dependent and will change with a horizontal or sitting position.)
Child (<8 years of age): 80-100 mm H2O (or 8-10 cm H2O)
Procedure
1. Measure the CSF pressure before any fluid is withdrawn.
2. Take up to four samples of 2 to 3 mL each, place in separate sterile vials, and label sequentially. Tube 1 is used for chemistry and serology; tube 2 is used for microbiology studies; tube 3 is used for hematology cell counts; and tube 4 is used for special studies.
Clinical Implications
1. Increases in CSF pressure can be a significant finding in the following conditions:
Intracranial tumors; abscess; lesions
Meningitis (bacterial, fungal, viral, or syphilitic)
Hypo-osmolality as a result of hemodialysis
Congestive heart failure
Superior vena cava syndrome
Subarachnoid hemorrhage
Cerebral edema
Thrombosis of venous sinuses
Conditions inhibiting CSF absorption
2. Decreases in pressure can be a significant finding in the following conditions:
Circulatory collapse
Severe dehydration
Hyperosmolality (increased osmotic concentration)
Leakage of spinal fluid
Spinal-subarachnoid block
3. Significant variations between opening and closing CSF pressure can be found in the following conditions:
Tumors or spinal blockage above the puncture site when there is a large pressure drop (no further fluid should be withdrawn)
Hydrocephalus when there is a small pressure drop that is indicative of a large CSF pool
Interfering Factors
1. Slight elevations of CSF pressure may occur in an anxious patient who holds his or her breath or tenses his or her muscles.
2. If the patient’s knees are flexed too firmly against the abdomen, venous compression will cause an elevation in CSF pressure. This can occur in patients of normal weight and in those who are obese.
Interventions
Pretest Patient Care
1. Follow pretest patient care for lumbar puncture.
2. Follow guidelines in Chapter 1 regarding safe, effective, informed pretest care.
Posttest Patient Care
1. Interpret abnormal pressure levels and monitor and intervene appropriately to prevent complications.
2. Follow posttest patient care for lumbar puncture.
3. Follow guidelines in Chapter 1 regarding safe, effective, informed posttest care.
CSF Color and AppearanceNormal CSF is crystal clear, with the appearance and viscosity of water. Abnormal CSF may appear hazy, cloudy, smoky, or bloody. Clotting of CSF is abnormal and indicates increased protein or fibrinogen levels.
The initial appearance of CSF can provide various types of diagnostic information. Inflammatory diseases, hemorrhage, tumors, and trauma produce elevated cell counts and corresponding changes in appearance.
Reference Values
Normal
Clear and colorless
Procedure
1. A lumbar puncture is performed (see Lumbar Puncture [Spinal Tap]).
2. Compare the CSF with a test tube of distilled water held against a white background. If there is no turbidity, newsprint can be read through normal CSF in the tube.
Clinical Implications
1. Abnormal appearance (Table 5.3)—causes and indications:
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