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 (ie, 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 (eg, K+, Ca2+, Mg2+), whereas other substances (eg, 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 (eg, 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 (L3L4 until 9 months of age, when the cord ascends to L1L2); therefore; a low lumbar puncture should be made in these patients.

Table 5.1 Normal CSF Values

• Volume • Adult: 90to150 mL; • child: 60to100 mL • Appearance Crystal clear, colorless • Pressure • Adult: 90to180 mm H2O;

• child: 10to100 mm H2O T

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:

• 1.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)

• 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 (eg, 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

Clinical Alert

• The MRZ reaction occurs in MS, lupus erythematosus, Sjogren'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 (eg, 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).

Table 5.2 Tumor Markers in CSF

• Alpha-fetoprotein (AFP) • CNS dysgerminomas and meningeal

carcinomas • <1.5 mg/mL (<1.5 µg/L)

alfa-Glucuronidase

• Possible meningeal adenocarcinoma • <49 mU/L (<0.82 nKat/L) normal; 47to70 mU/L

(0.78to1.17 nKat/L), suspicious• Acute myeloblastic leukemia • >70 mU/L (>1.17 nKat/L) abnormal

Carcinoembryonic antigen (CEA)

• Meningeal carcinomatosis; intradural or extradural, or brain parenchymal metastasis from adenocarcinoma; although the assay appears to be specific for adenocarcinoma and squamous cell carcinoma, increased CEA values in CSF are not seen in all such tumors of the brain <0.6 ng/mL (<0.6 µg/L)

Human chorionic gonadotropin (hCG)

• Adjunct in determining CNS dysgerminomas and meningeal carcinomatosis <0.21 U/L (<1.5 IU/L)

Lysozyme (muramidase)

• CNS tumors, especially myoclonal and monocytic leukemia 4to13 µg/mL (0.28to0.91 µmol/L)

Clinical Alert

• Blood levels for specific substances should always be measured simultaneously with CSF determinations for meaningful interpretation of results.

• Before lumbar puncture, check eyegrounds for evidence of papilledema because its presence may signal potential problems or complications of lumbar puncture.

• A mass lesion should be precluded by computed tomography (CT) scan before lumbar puncture because this can lead to brainstem herniation.

• 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 TestsLumbar Puncture (Spinal Tap)

Procedure

• 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.

• 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).

• Inject a local anesthetic slowly into the dermis around the intended puncture site.

• 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.

• 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.

• 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.

• Apply a small sterile dressing to the puncture site.• 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.

• Record procedure start and completion times, patient's status, CSF appearance, and CSF pressure readings.

• Procedural Alert• If the opening pressure is more than 200 mm

H2O in a relaxed patient, no more than 2 mL of CSF should be withdrawn.

• 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.

• Interventions• Pretest Patient Care• 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.

• 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.

• Follow guidelines in Chapter 1 regarding safe, effective, informed pretest care.

• Posttest Patient Care• 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.

• Women may have difficulty voiding in this position. The use of a fracture bedpan may help.

• Fluids are encouraged to help prevent or relieve headache, which is a possible result of lumbar puncture.

• Interpret test outcomes. Assess and monitor for abnormal outcomes and complications such as paralysis (or progression of paralysis, as with spinal tumor), hematoma, meningitis, P.318

• 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.

• 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.

• 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.

• Check the puncture site for leakage.• Document the procedure completion and any

problems encountered or complaints voiced by the patient.

• Follow guidelines in Chapter 1 regarding safe, effective, informed posttest care.

• Clinical Alert• Extreme caution should be used when performing lumbar

puncture:– If 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.

• 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

• If there is CSF leakage at the puncture site, notify the physician immediately and document findings.

• Follow standard precautions (see Appendix A) when handling CSF specimens.

• CSF Pressure• The 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.

• P.319

•Reference Values

• Normal• Adult: 90–180 mm 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): 10–100 mm H2O

• Procedure• Measure the CSF pressure before any fluid is

withdrawn.• 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• 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

• Decreases in pressure can be a significant finding in the following conditions:– Circulatory collapse– Severe dehydration– Hyperosmolality– Leakage of spinal fluid– Spinal-subarachnoid block

• 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• Slight elevations of CSF pressure may occur in an anxious patient who holds his or her

breath or tenses his or her muscles.• 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• Follow pretest patient care for lumbar puncture.• Follow guidelines in Chapter 1 regarding safe, effective, informed pretest care.• Posttest Patient Care• Interpret abnormal pressure levels and monitor and intervene appropriately to prevent

complications.• P.320

• Follow posttest patient care for lumbar puncture.• Follow guidelines in Chapter 1 regarding safe, effective, informed

posttest care.• CSF Color and Appearance• Normal 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• A lumbar puncture is performed (see Lumbar

Puncture [Spinal Tap]).• 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• Abnormal appearance (Table 5.3)—causes and indications:

– Blood. The blood is evenly mixed in all three tubes in subarachnoid and cerebral hemorrhage. Table 5.4 describes differentiation of bloody spinal tap from cerebral hemorrhage. Clear CSF fluid does not rule out intracranial hemorrhage.

– Turbidity is graded from 1+ (slightly cloudy) to 4+ (very cloudy) and may be caused by the following conditions:• Leukocytes (pleocytosis)• Erythrocytes• Microorganisms such as fungi and amebae• Protein

Table 5.3 Color Changes in CSF Suggestive of Disease States

• Opalescent, slightly yellow, with delicate clot Tuberculous meningitis• Opalescent to purulent, slightly yellow, with coarse clot Acute

pyogenic meningitis• Slightly yellow; may be clear or opalescent, with delicate clot Acute

anterior poliomyelitis• Bloody, purulent, may be turbid Primary amebic

meningoencephalitis• Generally clear, but may be xanthochromic Tumor of brain or cord• Xanthochromic Toxoplasmosis• Viscous Metastatic colon cancer, severe meningeal infection,

cryptococcus, injury

• Aspirated epidural fat (pale pink to dark yellow)• Contrast media

– Xanthochromia (pale pink to dark yellow) can be caused by the following conditions:• Oxyhemoglobin from lysed red blood cells (RBCs) present in CSF before lumbar

puncture• Methemoglobin• Bilirubin (>6 mg/dL or >103 µmol/L)• Increased protein (>150 mg/dL or >1500 mg/L)• Melanin (meningeal melanocarcinoma)• Carotene (systemic carotenemia)• Prior bleeding within 2–36 hours (eg, traumatic puncture >72 hours before)

– Yellow color (bilirubin, >10 mg/dL or >171 µmol/L) due to a prior hemorrhage (10 hours to 4 weeks before)

• Clinical Alert• Spinal fluid should be cultured for bacteria, fungi,

and tuberculosis. In children, Haemophilus influenzae type B is the most common cause of bacterial meningitis; in adults, the most common bacterial pathogens for meningitis are meningococci and pneumococci.

• Spinal fluid with any degree of cloudiness should be treated with extreme care because this could be an indication of contagious disease.

• Interfering Factors• CSF can look xanthochromic from

contamination with methylate used to disinfect the skin.

• If the blood in the specimen is due to a traumatic spinal tap, the CSF in the third tube should be clearer than that in tube 1 or 2; a traumatic tap makes interpretation of results very difficult to impossible.

• Interventions• Pretest Patient Care• Observations of color and appearance of CSF

are always noted.• See Lumbar Puncture procedure.• P.322

Posttest Patient Care

• Recognize abnormal color and presence of turbidity and monitor patient appropriately.

• See Lumbar Puncture procedure.

CSF Microscopic Examination of Cells; Total Cell Count; Differential Cell Count

• Normal CSF contains a small number of lymphocytes and monocytes in a ratio of approximately 70:30 in adults. A higher proportion of monocytes is present in young children. An increase in the number of white blood cells (WBCs) in CSF is termed pleocytosis. Disease processes may lead to abrupt increases or decreases in numbers of cells.

• CSF is examined for the presence of RBCs and WBCs. The cells are counted and identified by cell type; the percentage of cell type is compared with the total number of WBCs or RBCs present. In general, inflammatory disease, hemorrhage, neoplasms, and trauma cause an elevated WBC count.

• Reference Values• Normal• Normal CSF is essentially free of cells (Tables 5.5

and 5.6).• Adults: 0–5 WBCs/µL or 0–5 × 106 WBCs/L• Newborn: 0–30 WBCs/µL or 0–30 × 106

WBCs/L• Child: 0–15 WBCs/µL or 0–15 × 106

WBCs/L

• Clinical Alert• Critical Values• >20 segmented neutrophils• Procedure• A lumbar puncture is performed (see Lumbar

Puncture [Spinal Tap]).• Typically, approximately 20 mL of CSF is

obtained and subsequently divided into four separate tubes.

• One of the tubes is used for counting the cells present in the CSF sample. The cells are counted by a manual counting chamber or by electronic means. A CSF smear is made, and various types of cells present are counted to determine differentiation of cells.

• Clinical Implications• The total CSF cell count (includes neutrophils,

lymphocytes, mixed cells, and cells after hemorrhage) is the most sensitive index of acute inflammation of the CNS.

• WBC counts >500 WBCs/µL or >500 × 106 WBCs/L usually arise from a purulent infection and are preponderantly granulocytes (ie, neutrophils). Neutrophilic reaction classically suggests meningitis caused by a pyogenic organism, in which case the WBC count can exceed 1000 WBCs/µL or 1000 × 106 WBCs/L and even reach 20,000 WBCs/µL or 20,000 × 106 WBCs/L.

– Increases in neutrophils are associated with the following conditions:• Bacterial meningitis (see Table 5.7)• Early viral meningitis• Early tubercular meningitis• Fungal mycositic meningitis• Amebic encephalomyelitis• Early stages of cerebral abscess

– Noninfectious causes of neutrophilia include the following:• Reaction to CNS hemorrhage• Injection of foreign materials into the subarachnoid space

(eg, x-ray contrast medium, anticancer drugs)• CSF infarct• Metastatic tumor in contact with CSF• Reaction to repeated lumbar puncture

• P.324

• WBC counts of 300–500/µL or 300–500 × 106/L with preponderantly lymphocytes are indicative of the following conditions:– Viral meningitis– Syphilis of CNS (ie, meningoencephalitis)– Tuberculous meningitis– Parasitic infestation of the CNS– Bacterial meningitis due to unusual organisms (eg, Listeria species)– Multiple sclerosis (MS) (reactive lymph present)– Encephalopathy caused by drug abuse– Guillain-Barré syndrome (15%)– Acute disseminated encephalomyelitis– Sarcoidosis of meninges– Human T-lymphotropic virus type III (HTLV III)– P.325

– Aseptic meningitis due to peptic focus adjacent to meninges– Fungal meningitis– Polyneuritis

• WBC counts with ≥40% monocytes occur in the following conditions:– Chronic bacterial meningitis– Toxoplasmosis and amebic meningitis– MS– Rupture of brain abscess

• Malignant cells (lymphocytes or histiocytes) may be present with primary and metastatic brain tumors, especially when there is meningeal extension.

• Increased numbers of plasma cells occur in the following conditions:– Acute viral infections– MS– Sarcoidosis– Syphilitic meningoencephalitis– Subacute sclerosing panencephalitis– Tuberculous meningitis– Parasitic infestations of CSF– Guillain-Barré syndrome– Lymphocytic reactions

• Plasma cells are responsible for an increase in IgG and altered patterns in immunoelectrophoresis.

• Macrophages are present in tuberculous or viral meningitis and in reactions to erythrocytes, foreign substances, or lipids in the CSF.

• Ependymal and plexus cells may be present after surgical procedures or trauma to the CNS (not clinically significant).

• Blast cells appear in CSF when acute leukemia is present (lymphoblasts or myeloblasts).

• Eosinophils are present in the following conditions:– Parasitic infections– Fungal infections– Rickettsial infections (Rocky Mountain spotted fever)– Idiopathic hypereosinophilic syndrome– Reaction to foreign materials in CSF (eg, drugs,

shunts)– Sarcoidosis

• Clinical Alert• Neutrophilic reaction classically suggests

meningitis caused by a pyogenic organism.• Interventions

• Pretest Patient Care• See Lumbar Puncture procedure.• Follow guidelines in Chapter 1 regarding safe,

effective, informed pretest care.

• Posttest Patient Care• Interpret abnormal cell counts. Monitor,

intervene, and counsel as appropriate for infection and malignancy.

• See Lumbar Puncture procedure.• Follow guidelines in Chapter 1 regarding safe,

effective, informed posttest care.

• CSF Glucose• The CSF glucose level varies with the blood glucose levels. It is usually

about 60% of the blood glucose level. A blood glucose specimen should be obtained at least 60 minutes before lumbar puncture for comparisons. Any changes in blood sugar are reflected in the CSF approximately 1 hour later because of the lag in CSF glucose equilibrium time.

• P.326•

This measurement is helpful in determining impaired transport of glucose from plasma to CSF, increased use of glucose in the CNS, and glucose utilization by leukocytes and microorganisms. The finding of a markedly decreased CSF glucose level accompanied by an increased WBC count with a large percentage of neutrophils is indicative of bacterial meningitis.

• Reference Values

• Normal• Adult: 40–70 mg/dL or 2.2–3.9 mmol/L• Child: 60–80 mg/dL or 3.3–4.4 mmol/L• CSF-to-plasma glucose ratio: <0.5• CSF glucose level: 60%–70% of blood

glucose levels

• Clinical Alert• The critical value for CSF glucose level is <20 mg/dL (<1.1

mmol/L); below this level, damage to the CNS will occur.• Procedure• A lumbar puncture is performed (see Lumbar Puncture

[Spinal Tap]).• Place 1 mL of CSF in a sterile tube. The glucose test should

be done on tube 1 when three tubes of CSF are taken. Accurate evaluation of CSF glucose requires a plasma glucose measurement. A blood glucose level ideally should be drawn 1 hour before the lumbar puncture.

• Clinical Implications• Decreased CSF glucose levels are associated

with the following conditions:– Acute bacterial meningitis– Tuberculous, fungal, and amebic meningitis– Systemic hypoglycemia– Subarachnoid hemorrhage

• CSF glucose levels are uncommonly decreased in the following conditions:– Malignant tumor with meningeal involvement– Acute syphilitic meningitis– Nonbacterial meningoencephalitis

• Increased CSF glucose levels are associated with the following conditions:– Diabetic hyperglycemia– Increased serum glucose– Epidemic encephalitis

• Clinical Alert• All types of organisms consume glucose; therefore, decreased glucose levels

reflect abnormal activity.• The findings of a markedly decreased CSF glucose and an increased WBC count

with a high percentage of neutrophils are indicative of bacterial meningitis.• Interfering Factors• Falsely decreased levels may be due to cellular and bacterial metabolism if the

test is not performed immediately after specimen collection.• A traumatic tap may produce misleading results owing to glucose present in

blood.• See Appendix E for drugs that affect test outcomes.• P.327

• Interventions• Pretest Patient Care• See Lumbar Puncture procedure.• Explain the need for a blood specimen test for glucose to compare with CSF

glucose.• Follow guidelines in Chapter 1 regarding safe, effective, informed pretest

care.• Posttest Patient Care• Interpret abnormal CSF glucose levels and correlate with the presence of

meningitis, cancer, hemorrhage, and diabetes. Monitor and intervene appropriately to prevent complications.

• P.328

• See Lumbar Puncture procedure.• Follow guidelines in Chapter 1 regarding safe, effective, informed posttest care.• CSF Glutamine• Glutamine, an amino acid, is synthesized in brain tissue from ammonia and α-

ketoglutarate. Production of glutamine, the most prominent amino acid in CSF, provides a mechanism for removing the ammonia, a toxic metabolic waste product, from the CNS.

• The determination of CSF glutamine level provides an indirect test for the presence of excess ammonia in the CSF. As the concentration of ammonia in the CSF increases, the supply of α-ketoglutarate becomes depleted; consequently, glutamine can no longer be produced to remove the toxic ammonia, and coma ensues. A CSF glutamine test is therefore frequently requested for patients with coma of unknown origin.

• Reference Values• Normal• 8.6 ± 0.50 mg/dL or 0.60 ± 0.03 mmol/L or 590 ±

34 µmol/L (A CSF glutamine value >35 mg/dL [>2.4 mmol/L] usually results in loss of consciousness.)

• Procedure• A lumbar puncture is performed (see Lumbar Puncture

[Spinal Tap]).• Use 1 mL of CSF for the glutamine test.• Centrifuge the samples if cells are present.

• Clinical Implications• Increased CSF glutamine levels are associated

with the following conditions:• Hepatic encephalopathy (glutamine values

>35 mg/dL or >2.4 mmol/L are diagnostic)• Reye's syndrome• Encephalopathy secondary to hypercapnia or

sepsis

• Bacterial meningitis• Interventions• Pretest Patient Care• See Lumbar Puncture procedure.• Follow guidelines in Chapter 1 regarding safe,

effective, informed pretest care.

• Posttest Patient Care• Interpret abnormal glutamine levels and correlate with clinical symptoms. Monitor

and intervene appropriately to prevent complications.• See Lumbar Puncture procedure.• Follow guidelines in Chapter 1 regarding safe, effective, informed posttest care.• CSF Lactic Acid, L-Lactate• The source of CSF lactic acid (L-lactate) is CNS anaerobic metabolism. Lactic acid in

CSF varies independently with the level of lactic acid in the blood. Destruction of tissue within the CNS because of oxygen deprivation causes the production of increased CSF lactic acid levels. Thus, elevated CSF lactic acid levels can result from any condition that decreases the flow of oxygen to brain tissues.

• The CSF lactic acid test is used to differentiate between bacterial and nonbacterial meningitis. Elevated CSF lactate levels are not limited to meningitis and can result from any condition that decreases the flow of oxygen to the brain. CSF lactate levels are frequently used to monitor severe head injuries.

• Reference Values

• Normal• Adult: 10–22 mg/dL or 1.1–2.4 mmol/L• Newborn: 10–60 mg/dL or 1.1–6.7 mmol/L• Procedure• A lumbar puncture is performed (see Lumbar Puncture [Spinal Tap]).• Collect 0.5 mL of CSF in a sterile test tube.• Refrigerate the sample.• Clinical Implications• Increased CSF lactic acid levels are associated with the following

conditions:• Bacterial meningitis (>38 mg/dL or >4.2 mmol/L)• Brain abscess or tumor

• Cerebral ischemia• Cerebral trauma• Seizures• Stroke (cerebral infarct)• Increased intracranial pressure• Note• Generally, in viral meningitis the CSF lactic acid will be <38 mg/dL

or <4.2 mmol/L.• Interfering Factors• Traumatic tap causes elevated levels: RBCs contain large amounts

of lactate. Hemolyzed or xanthochromic specimens will give falsely elevated results.

• Interventions• Pretest Patient Care• See Lumbar Puncture procedure.• Follow guidelines in Chapter 1 regarding safe, effective, informed

pretest care.• Posttest Patient Care• Interpret test outcomes; monitor and intervene appropriately to

detect CNS disease and prevent complications. Results must be interpreted in light of clinical symptoms.

• P.329

• See Lumbar Puncture procedure.• Follow guidelines in Chapter 1 regarding safe, effective,

informed posttest care.• Clinical Alert• Increases in CSF lactic acid levels must be interpreted in

light of the clinical findings and in conjunction with glucose levels, protein levels, and cell counts in the CSF. Equivocal results in some instances of aseptic meningitis may lead to erroneous diagnosis of a bacterial etiology. Increased lactate in CSF following head injury suggests poor prognosis

• CSF Lactate Dehydrogenase (LD/LDH); CSF Lactate Dehydrogenase (LDH) Isoenzymes

• Although many different enzymes have been measured in CSF, only lactate dehydrogenase (LDH) appears useful clinically. Sources of LDH in normal CSF include diffusion across the blood-CSF barrier, diffusion across the brain-CSF barrier, and LDH activity in cellular elements of the CSF, such as leukocytes, bacteria, and tumor cells. Because brain tissue is rich in LDH, damaged CNS tissue can cause increased levels of LDH in the CSF.

• High levels of LDH occur in about 90% of cases of bacterial meningitis and in only 10% of cases of viral meningitis. When high levels of LDH do occur in viral meningitis, the condition is usually associated with encephalitis and a poor prognosis. Tests of LDH isoenzymes have been used to improve the specificity of LDH measurements and are useful for making the differential diagnosis of viral versus bacterial meningitis (see Chapter 6 for a complete description of isoenzymes). Elevated LDH levels following resuscitation predict a poor outcome in patients with hypoxic brain injury.

• Reference Values• Normal• Adults: <40 U/L or approximately 10% of serum levels (total LD activity)• Neonates: <70 U/L

• Note• Depending on the upper limit or cut-off value,

sensitivity and specificity can vary between 70% and 85%.

• Procedure• A lumbar puncture is performed (see Lumbar

Puncture [Spinal Tap]).• Obtain 1 mL of CSF for the LDH test.• Take the sample to the laboratory as quickly as

possible.

• Clinical Implications• Increased CSF LDH levels are associated with the following conditions:

– Bacterial meningitis (90% of cases)– Viral meningitis (10% of cases)– Massive cerebrovascular accident– Leukemia or lymphoma with meningeal infiltration– Metastatic carcinoma of the CNS

• The presence of CSF LDH isoenzymes 1, 2, and 3 reflects a CNS lymphocytic reaction, suggesting viral meningitis.

• The CSF LDH isoenzyme pattern reflects a granulocytic (neutrophilic) reaction with LDH isoenzymes 4 and 5, suggesting bacterial meningitis.

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• High levels of CSF LDH isoenzymes 1 and 2 suggest extensive CNS damage and a poor prognosis (ie, they are indicative of destruction of brain tissue).

• CSF LDH isoenzymes 3 and 4 suggest lymphatic leukemia or lymphoma.• Interfering Factors• For the LDH test to be valid, CSF must not be contaminated with blood. A traumatic

lumbar tap will make results difficult to interpret.• Interventions• Pretest Patient Care• See Lumbar Puncture procedure.• Follow guidelines in Chapter 1 regarding safe, effective, informed pretest care.• Posttest Patient Care• Interpret abnormal LDH test patterns and monitor and intervene appropriately to

detect and prevent complications.• See Lumbar Puncture procedure.• Follow guidelines in Chapter 1 regarding safe, effective, informed posttest care.

• CSF Total Protein• The CSF normally contains very little protein because the protein

in the blood plasma does not cross the blood-brain barrier easily. Protein concentration normally increases caudally from the ventricles to the cisterns and finally to the lumbar sac.

• The CSF protein is a nonspecific but reliable indication of CNS pathology such as meningitis, brain abscess, MS, and other degenerative processes causing neoplastic disease. Elevated CSF protein levels may be caused by increased permeability of the blood-brain barrier, decreased resorption of the arachnoid villi, mechanical obstruction of the CSF flow, or increased intrathecal immunologic synthesis.

• Reference Values

• Normal• Results vary by method used; check with the laboratory for reference values.• Total protein:• Adults: 15–45 mg/dL or 150–450 mg/L (lumbar)• Adults: 15–25 mg/dL or 150–250 mg/L (cisternal)• Adults: 5–15 mg/dL or 50–150 mg/L (ventricular)• Neonates: 15–100 mg/dL or 150–1000 mg/L (lumbar)• Elderly patients (>60 years of age): 15–60 mg/dL or 150–600 mg/L (lumbar)• Clinical Alert• Critical Values• Low: none• High: >45 mg/mL or >450 mg/L in the adult• Procedure• A lumbar puncture is performed (see Lumbar Puncture [Spinal Tap]).• Obtain 1 mL of CSF for protein analysis.• Measure serum protein levels concurrently to interpret CSF protein values.• P.331

• Clinical Implications• Increased CSF protein occurs in the following situations:

– Traumatic tap with normal CSF pressure: CSF initially streaked with blood, clearing in subsequent tubes

– Increased permeability of blood-CSF barrier (“influx syndromeâ€): CSF protein 100–500 mg/dL (1000–5000 �mg/L)• Infectious conditions

– Bacterial meningitis: Gram stain usually positive; culture may be negative if antibiotics have been administered

– Tuberculosis: CSF protein 50–300 mg/dL (500–3000 mg/L); mixed cellular reaction typical

– Fungal meningitis: CSF protein 50–300 mg/dL (500–3000 mg/L); special stains helpful

– Viral meningitis: CSF protein usually <200 mg/dL (<2000 mg/L)

• Noninfectious conditions– Subarachnoid hemorrhage: xanthochromia 2–4 hours after onset– Intracerebral hemorrhage: CSF protein 20–200 mg/dL

(200–2000 mg/L); marked fall in pressure after removing small amounts of CSF; xanthochromia

– Cerebral thrombosis: slightly increased CSF protein in 40% of cases (usually, <100 mg/dL or <1000 mg/L)

– Endocrine disorders, diabetic neuropathy, myxedema, hyperadrenalism, hypoparathyroidism: CSF protein 50–150 mg/dL (500–1500 mg/L) in about 50% of cases

– Metabolic disorders, uremia, hypercalcemia, hypercapnia, dehydration: CSF protein slightly elevated (usually, <100 mg/dL or <1000 mg/L)

– Drug toxicity, ethanol, phenytoin, phenothiazines: CSF protein slightly elevated in about 40% of cases (usually, <200 mg/dL or <2000 mg/L)

– Obstruction to circulation of CSF occurs in the following circumstances:• Mechanical obstruction (eg, tumor, abscess), herniated disk: rapid

fall in pressure (yellow CSF, contains excess protein)• Loculated effusion of CSF: repeated taps may show a progressive

increase in CSF protein; diagnosis by myelography

– Increased CSF IgG synthesis occurs in the following conditions:• MS: CSF protein level slightly increased• Subacute sclerosing panencephalitis: increased CSF protein• Neurosyphilis: CSF protein normal or slightly increased (usually, <100

mg/dL or <1000 mg/L)

– Increased CSF IgG synthesis and increased permeability of blood-CSF barrier occur in the following conditions:• Guillain-Barré syndrome (infectious polyneuritis): CSF protein

usually 100–400 mg/dL (1000–4000 mg/L)• Collagen diseases (eg, periarteritis, lupus): CSF protein usually <400

mg/dL (or <4000 mg/L)• Chronic inflammatory demyelinating polyradiculopathy

– Decreased CSF protein occurs in the following conditions:• Leakage of CSF due to trauma• Removal of a large volume of CSF• Intracranial hypertension• Hyperthyroidism• Young children between 6 months and 2 years of age

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Clinical Alert• More than 1000 mg/dL (>10,000 mg/L) of protein in CSF

suggests subarachnoid block. In a complete spinal block, the lower the tumor location, the higher the CSF protein value.

• Interfering Factors• Hemolyzed or xanthochromic drugs may falsely depress results.• Traumatic tap will invalidate the protein results.• See Appendix E for drugs that affect test outcomes.• Interventions

• Pretest Patient Care• See Lumbar Puncture procedure.• Follow guidelines in Chapter 1 regarding safe,

effective, informed pretest care.• Posttest Patient Care• Interpret abnormal CSF protein levels; monitor for

both infectious and noninfectious conditions and intervene appropriately to prevent and detect complications.

• See Lumbar Puncture procedure.

• Follow guidelines in Chapter 1 regarding safe, effective, informed posttest care.

• CSF Albumin and Immunoglobulin G (IgG)• Albumin composes most (50%–75%) of the proteins in CSF. The albumin and

IgG that are present in normal CSF are derived from the serum. Increased levels of either or both are indicative of damage to the blood-CNS barrier.

• The combined measurement of albumin and IgG is used to evaluate the integrity and permeability of the blood-CSF barrier and to measure the synthesis of IgG within the CNS. The IgG index is the most sensitive method to determine local CNS synthesis of IgG and to detect increased permeability of the blood-CNS barrier.

• The IgG index method is superior to the IgG-to-albumin ratio or measurement of IgG only.

• Reference Values

• Normal• Albumin: 10–35 mg/dL or 1.5–5.3 µmol/L• IgG: <4.0 mg/dL or <40 mg/L• CSF serum albumin index: <9.0• CSF IgG index: <0.60• CSF IgG index = (CSF IgG × serum albumin)/(Serum IgG × CSF

albumin)• CSF-to-serum IgG ratio: <0.003• Procedure• A lumbar puncture is performed (see Lumbar Puncture [Spinal Tap]).• Obtain 0.5 mL of CSF in a sterile tube.• Freeze the sample if the determination is not done immediately.

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Clinical Implications• Increased CSF albumin occurs in most of the same conditions

as increased total protein, especially:РLesions of the choroid plexusРBlockage of CSF flowРBacterial meningitisРGuillain-Barr̩ syndromeРMany infectious diseases, such as typhoid fever, tularemia,

diphtheria, and septicemia– Malignant neoplasms of the CNS

• CSF serum albumin index:– An index of <9.0 is consistent with an intact blood-brain barrier– An index between 9 and 14 is considered slight impairment to the

barrier.– An index from 14 to 30 is considered moderate impairment of the

barrier.– An index >30 is severe impairment.

• Increased CSF IgG index occurs in the following conditions:– MS– Subacute sclerosing leukoencephalitis– Neurosyphilis– Chronic phases of CNS infections (subacute sclerosing panencephalitis

[SSPE])

• Interfering Factors• A traumatic tap will invalidate the results.• Interventions• Pretest Patient Care• See Lumbar Puncture procedure.• Follow guidelines in Chapter 1 regarding safe, effective, informed pretest

care.• Posttest Patient Care• Interpret test outcomes; monitor and intervene appropriately to prevent

and detect complications.• See Lumbar Puncture procedure.• Follow guidelines in Chapter 1 regarding safe, effective, informed

posttest care.

• CSF Protein Electrophoresis; Oligoclonal Bands; Multiple Sclerosis Panel• Agarose gel electrophoresis of concentrated CSF is used to detect oligoclonal

bands, defined as two or more discrete bands in the γ region that are absent or of less intensity than in the concurrently tested patient's serum.

• Fractionation (ie, electrophoresis) of CSF is used to evaluate bacterial and viral infections and tumors of the CNS. However, the most important application of CSF protein electrophoresis is the detection and diagnosis of MS. Abnormalities of CSF in MS include an increase in total protein, primarily from IgG, which is the main component of the γ-globulin fraction. Abnormal immunoglobulins migrate as discrete, sharp bands, called oligoclonal bands. This is the pattern observed in MS: a pattern of discrete bands within the γ-globulin portion of the electrophoretic pattern. However, oligoclonal bands are found in the CSF of patients with other types of nervous system disorders of the immune system, including human immunodeficiency virus (HIV).

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Electrophoresis is also the method of choice to determine whether a fluid is actually CSF. Identification can be made based on the appearance of an extra band of transferrin (referred to as TAV), which occurs in CSF and not in serum.

• Reference Values• Normal• Globulins:• Oligoclonal banding: none present• α1-Globulin: 2%–7% (0.02–0.07)

• α1-Globulin: 4%–12% (0.04–0.12)• β-Globulin: 8%–18% (0.08–0.18)• γ-Globulin: 3%–12% (0.03–0.12)• Prealbumin: 2%–7%; (0.02–0.07)• Albumin: 56%–76% (0.56–0.76)• IgA: 0.10 mg/dL or 1.0 mg/L• IgD: 3.0 U/mL or 3.0 kU/L• IgG: 5.0 mg/dL or 50 mg/L• IgG synthesis rate: 0.0–8.0 mg/24 hours (average is 3.0) or 0.0–8.0 mg/day• IgG-to-albumin ratio: 0.09–0.25• IgM: 0.017 mg/dL or 0.17 mg/L

• Procedure• A lumbar puncture is performed (see Lumbar Puncture

[Spinal Tap]).• Obtain 3 mL of CSF for this test. The sample must be

frozen if the test is not performed immediately.• Apply a sample of the concentrate to a thin-layer

agarose gel. Subject the agarose gel to electrophoresis. CSF is concentrated approximately 80-fold by selective permeability. Serum electrophoresis must be done concurrently for interpretation of the bands.

• Clinical Implications• Increases in CSF IgG or in the IgG-to-albumin

index occur in the following conditions:РMSРSubacute sclerosing panencephalitisРTumors of the brain and meningesРChronic CNS infectionsРSome patients with meningitis, Guillain-Barr̩

syndrome, lupus erythematosus involving the CNS, and other neurologic conditions

• Increases in the CSF albumin index occur in the following conditions:– Obstruction of CSF circulation– Damage to the CNS blood-brain barrier– Diabetes mellitus– Systemic lupus erythematosus of the CNS– Guillain-Barré syndrome– Polyneuropathy– Cervical spondylosis

• Increased CSF γ-globulin and the presence of oligoclonal bands occur in the following conditions:– MS– Neurosyphilis– P.335

РSubacute sclerosing panencephalitisРCerebral infarctionРViral and bacterial meningitisРProgressive rubella panencephalitisРCryptococcal meningitisРIdiopathic polyneuritisРBurkitt's lymphomaРHIV-1 (acquired immunodeficiency syndrome [AIDS])РGuillain-Barr̩ syndrome

• Increased CSF synthesis of IgG occurs in the following conditions:– MS (90% of definite cases)– Inflammatory neurologic diseases– Postpolio syndrome

• Clinical Alert• A serum electrophoresis must be done at the same time as the CSF

electrophoresis. An abnormal result is the finding of two or more bands in the CSF that are not present in the serum specimen (Fig. 5.3).

• Oligoclonal bands are not specific for multiple sclerosis; however, the sensitivity is 83% to 94%. (0.83 to 0.94).

• Diagnostic differentiation between MS and CSF autoimmune disease relies on further testing (eg, antinuclear antibodies [ANAs] in blood [see Chapter 8]).

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• Interfering Factors• A traumatic tap invalidates the results.• Recent myelography affects the results.• Interventions

• Pretest Patient Care• See Lumbar Puncture procedure.• Follow guidelines in Chapter 1 regarding safe,

effective, informed pretest care.• Posttest Patient Care• Interpret test outcome; monitor for MS and

other CNS disorders and intervene appropriately to prevent and detect complications.

• See Lumbar Puncture procedure.• Follow guidelines in Chapter 1 regarding safe,

effective, informed posttest care.

• CSF Syphilis Serology• Reference Values• Normal• Negative (ie, nonreactive) for syphilis. Neurosyphilis

is characterized by an increase in protein, an increase in the number of lymphocytes, and a positive test for syphilis (see Chapter 8). Use CSF VDRL test, only if serum VDRL test is positive, to rule in, not rule out, neurosyphilis. Do not use VDRL to evaluate the results of syphilis therapy.