Cerebrospinal fluid (CSF) is a clear watery liquid filtrate that is formed and secreted by the choroid plexus, special tissue that has many blood vessels and lines the small cavities or chambers (ventricles) in the brain. CSF flows around the brain and spinal cord, surrounding and protecting them. It is continually produced, circulated, and then absorbed into the blood system. About 500 mL is produced each day. This rate of production means that all of the CSF is replaced every few hours.
A protective blood-brain barrier separates the brain from circulating blood and regulates the distribution of substances between the blood and the CSF. It helps keep large molecules, toxins, and most blood cells away from the brain. Any condition that disrupts this protective barrier may result in a change in the normal level or type of constituents of CSF. Because CSF surrounds the brain and spinal cord, testing a sample of CSF can be very valuable in diagnosing a variety of conditions affecting the central nervous system (CNS). Though a sample of CSF may be more difficult to obtain than, for example, urine or blood, the results may reveal more directly the cause of CNS symptoms.
For example, infections and inflammation in the meninges (called meningitis) or the brain (called encephalitis) can disrupt the blood-brain barrier and allow white and red blood cells and increased amounts of protein into the CSF. Meningitis and encephalitis can also lead to the production of antibodies. Immune diseases that affect the CNS, such as Guillain-Barré Syndrome, and multiple sclerosis can also produce antibodies that can be found in the CSF. Cancers such as leukemia can lead to an increase in CSF white blood cells (WBCs), and cancerous tumors can result in the presence of abnormal cells. These changes from normal CSF constituents make the examination of cerebrospinal fluid valuable as a diagnostic tool.
CSF analysis usually involves an initial basic set of tests performed when CSF analysis is requested:
- CSF color, clarity and pressure during collection
- CSF protein
- CSF glucose
- CSF cell count
- CSF differential
- If infection is suspected, CSF gram stain and culture
A wide variety of other tests may be ordered as follow-up depending on the results of the first set of tests. The specific tests that are ordered may also depend on the signs and symptoms of the patient and the disease the doctor suspects is the cause. Each of these tests can be grouped according to the type of exam that is performed:
- Physical characteristics —includes measurement of the pressure during sample collection and the appearance of the CSF.
- Chemical tests —this group refers to those tests that detect or measure the chemical substances found in spinal fluid. CSF is basically an ultafiltrate of the blood, so it can also be affected by what is going on in the blood. Normally, certain constituents of CSF such as protein and glucose are a percentage of blood levels, so CSF levels are often evaluated in relation to blood levels.
- Microscopic examination (Cell count and differential)—any cells that may be present are counted and identified by cell type under a microscope.
- Infectious disease tests —numerous tests can be done to detect and identify microorganisms if an infection is suspected.
How is the sample collected for testing?
A sample of cerebrospinal fluid (CSF) is collected by a doctor from the lower back using a procedure called a lumbar puncture or spinal tap. Often, three or more separate tubes of CSF are collected, and multiple tests may be run on the different samples.
Is any test preparation needed to ensure the quality of the sample?
The patient should empty their bladder and bowels prior to the sample collection. It will be necessary to lie still in a curled-up fetal position during the test and to lie quietly for a time period after the collection.
How is it used?
Cerebrospinal fluid (CSF) analysis may be used to help diagnose a wide variety of diseases and conditions affecting the central nervous system (CNS). They may be divided into four main categories:
- Infectious diseases such as meningitis and encephalitis—testing is used to determine if the cause is bacterial, tuberculous, fungal or viral, and to distinguish it from other conditions; may also be used to detect infections of or near the spinal cord or to investigate a fever of unknown origin.
- Bleeding (hemorrhaging) within the brain or skull
- Diseases that cause inflammation or other immune responses such as antibodies—these may include autoimmune disorders such as Guillain-Barré syndrome or sarcoidosis or diseases that cause the destruction of myelin such as multiple sclerosis
- Tumors located within the CNS (primary) or metastatic cancer
When is it ordered?
CSF analysis may be ordered when a doctor suspects that a patient has a condition or disease involving their CNS. A patient’s medical history may prompt the request for CSF analysis. It may be ordered when a patient has suffered trauma to the brain or spinal cord, has been diagnosed with cancer that may have spread (metastatic) or has signs or symptoms suggestive of a condition involving their CNS.
The signs and symptoms of CNS conditions can vary widely and many overlap with a variety of diseases and disorders. They may have sudden onset, suggesting an acute condition such as CNS bleeding or infection or may be slow to develop, indicating a chronic disease such as cancer or multiple sclerosis.
Depending on a patient’s history, doctors may order CSF analysis when some combination of the following signs and symptoms appear:
- changes in mental status and consciousness
- confusion, hallucinations or seizures
- muscle weakness or lethargy, fatigue
- flu-like symptoms that intensify over a few hours to a few days
- fever or rash
- sudden, severe or persistent headache or a stiff neck
- sensitivity to light
- numbness or tremor
- difficulties with speech
- difficulty walking, lack of coordination
- mood swings, depression
- infants may be irritable, cry when they are held, have body stiffness, refuse food, and have bulging fontanels (the soft spots on the top of the head)
What does the test result mean?
CSF usually contains a small amount of protein and glucose and may have a few white blood cells (WBCs).
Any condition that disrupts the normal pressure or flow of CSF or the protective ability of the blood/brain barrier can result in abnormal results of CSF testing. For detailed explanations of what various tests results may mean, see the sections on:
- CSF physical characteristics
- CSF chemical tests
- CSF microscopic examination
- CSF infectious disease tests
Is there anything else I should know?
Multiple tubes of CSF are often collected during a lumbar puncture to ensure the quality of samples for testing.
Bacterial and amoebic meningitis are medical emergencies. Your doctor must rapidly distinguish between these conditions, the generally more mild viral meningitis, and other conditions. Because prompt treatment is crucial, your doctor may start you on a broad-spectrum antibiotic before the diagnosis has been definitely determined.
To help diagnose your illness your doctor may want to know what recent illnesses and vaccinations you may have had, what symptoms you are experiencing, whether you have been in contact with any ill people, and what places you have recently traveled to.
What is a lumbar puncture (spinal tap) and how is it performed?
The lumbar puncture is a special but relatively routine procedure. It is usually performed while you are lying on your side in a curled up fetal position, but may sometimes be performed in a sitting position. It is crucial that you remain still during the procedure. Once you are in the correct position, your back is cleaned with an antiseptic and a local anesthetic is injected under the skin. When the area has become numb, a special needle is inserted through the skin, between two vertebrae, and into your spinal canal. It is gently advanced until it enters the subarachnoid space (located between the arachnoid and pia mater layers of the meninges) and cerebrospinal fluid (CSF) begins to flow. You may be asked to straighten out your legs at this point and relax your muscles. It is important not to move unless you are instructed to do so. An "opening" or initial pressure reading of the CSF is obtained. The doctor then collects a small amount of CSF in multiple sterile vials. A "closing" pressure is obtained, the needle is withdrawn, and a sterile dressing and pressure are applied to the puncture site. You will then be asked to lie quietly in a flat position, without lifting your head, for one or more hours to avoid a potential post-test spinal headache.
The lumbar puncture procedure usually takes less than half an hour. For most patients it is a moderately uncomfortable to somewhat painful procedure. The most common sensation is a feeling of pressure when the needle is introduced. Let your doctor know if you experience a headache or any abnormal sensations, such as pain, numbness, or tingling in your legs, or pain at the puncture site.
The lumbar puncture is performed low in the back, well below the end of the spinal cord, usually between lumbar (L) vertebrae L4 and L5. There are spinal nerves in the location sampled, but they have room to move away from the needle. There is the potential for the needle to contact a small vein on the way in. This can cause a "traumatic tap," which just means that a small amount of blood may leak into one or more of the samples collected. While this is not ideal, it may happen a certain percentage of the time. The evaluation of your results will take this into account.
Blood from the collection procedure (spinal tap) may contaminate the first portion of CSF sample that is collected. However, there are usually three or more separate tubes used to collect CSF samples during one spinal tap procedure. The last tube that is collected during a spinal tap is least likely to have blood cells present due to the procedure and is usually the sample used to test for the presence of blood cells in the CSF. Likewise, the last sample collected is used for infectious disease testing since it will not be contaminated with microorganisms from inserting the needle through the skin.
Are there other reasons to do a lumbar puncture?
Why do I need a spinal tap? Why can't my blood or urine be tested?
Spinal fluid, obtained during a spinal tap, is often the best sample to use for conditions affecting your central nervous system because your CSF surrounds your brain and spinal cord. Changes in the elements of your CSF due to CNS diseases or other serious conditions are often first and most easily detected in a sample of your spinal fluid. Tests on blood and urine may be used in conjunction with CSF analysis to evaluate your condition.
What other tests may be done in addition to CSF analysis?
Other laboratory testing that may be ordered along with or following CSF testing includes:
- Blood culture to detect and identify bacteria in the blood
- Cultures of other parts of the body to detect the source of the infection that led to meningitis or encephalitis
- Blood glucose, total protein to compare with the concentration of CSF glucose and protein
- CBC (complete blood count) to evaluate cell counts in blood
- Antibodies for a variety of viruses, such as West Nile Virus
- ESR (Erythrocyte Sedimentation Rate) and CRP (C-reactive Protein), indication of inflammation
- CMP (Comprehensive Metabolic Panel), a group of tests used to evaluate electrolyte balance and organ function
The appearance of the sample of CSF is usually compared to a sample of water.
- Pressure of the CSF can be measured when opening (starting) and closing (finishing) the collection.
- Increased CSF pressure may be seen with a variety of conditions that increase pressure within the brain or skull and/or that obstruct the flow of CSF, such as tumors, infection, abnormal accumulation of CSF within the brain (hydrocephalus), or bleeding.
- Decreased pressure may be due to dehydration, shock, or leakage of CSF through an opening (another LP site or sinus fracture).
- Color of the fluid — normal is clear and colorless. Changes in the color of the CSF are not diagnostic but may point to additional substances in the fluid. Yellow, orange, or pink CSF is said to be xanthochromic. It may indicate the breakdown of blood cells due to bleeding into the CSF or the presence of bilirubin. Green CSF may also sometimes be seen with bilirubin or infection.
- Turbidity — Cloudy or turbid CSF may indicate the presence of white or red blood cells, microorganisms, or an increase in protein levels.
- Viscosity — Normal CSF will have the same consistency as water. CSF that is “thicker” may be seen in patients with certain types of cancers or meningitis.
- Pressure of the CSF can be measured when opening (starting) and closing (finishing) the collection.
A few routine tests are usually performed on CSF samples.
- CSF glucose – normal is about 2/3 the concentration of blood glucose. Glucose levels may decrease when cells that are not normally present use up (metabolize) the glucose. These may include bacteria or cells present due to inflammation (WBCs) or shed by tumors.
- CSF protein – only a small amount is normally present in CSF because proteins are large molecules and do not cross the blood/brain barrier easily. Decreases in CSF protein are not generally considered significant. Increases in protein are most commonly seen with:
If any of the initial tests are abnormal or if the doctor has reason to suspect a specific condition, then additional testing may be ordered. This may include one or more of the following:
- CSF protein electrophoresis — separates different types of protein. Oligoclonal bands may be seen with multiple sclerosis and Lyme disease.
- CSF IgG (Immunoglobulin G) — increased in some conditions, such as multiple sclerosis, herpes encephalitis, connective tissue diseases.
- Myelin basic protein — seen when the covering of nerves (myelin) breaks down, such as with multiple sclerosis.
- CSF lactic acid — often used to distinguish between viral and bacterial meningitis. The level will usually be increased with bacterial and fungal meningitis while it will remain normal or only slightly elevated with viral meningitis.
- CSF lactate dehydrogenase (LD) — used to differentiate between bacterial and viral meningitis; may also be elevated with leukemia or stroke.
- CSF glutamine — may be increased with liver disease: hepatic encephalopathy and Reye syndrome
- CSF C-reactive protein (CRP) is an acute phase reactant and is elevated with inflammation. It is markedly increased with bacterial meningitis. Since it is very sensitive even with early bacterial meningitis, it is often used to distinguish between bacterial and viral meningitis.
- Tumor markers — Carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), and hCG may be increased in cancers that have spread from other sites in the body (metastatic).
Infectious disease tests
- CSF gram stain for direct observation of microorganisms under a microscope. There should be no microorganisms in CSF fluid. If bacteria or fungi are present on a CSF gram stain, then the patient has bacterial or fungal meningitis or encephalitis.
- CSF culture and sensitivity is used to detect any microorganisms, which will grow in the culture. If bacteria are present, they can be tested in the laboratory to predict the best choices for antimicrobial therapy for the patient and prophylaxis of close contacts, if needed. If there are no microorganisms present, it does not rule out an infection; they may be present in small numbers or unable to grow in culture due to prior antibiotic therapy.
If any of the initial tests are abnormal or if the doctor strongly suspects a CNS infection, then additional testing may be ordered. This may include one or more of the following:
- Detection of viruses – detection of viral genetic material (DNA, RNA) by PCR testing; for example, herpes virus and enteroviruses. Positive PCR tests for viral DNA or RNA, antigen tests, and growth on viral cultures indicate that the patient has a viral infection and may have viral encephalitis or meningitis. The presence of viral antibodies and their increase over time indicates a recent infection by that virus (such as a four-fold increase in the titer of West Nile Virus antibody in samples drawn several weeks apart).
- CSF Cryptococcal antigen – to detect a specific fungal infection
- Other CSF antigen tests – depending on which organism(s) are suspected
- Specific CSF antibody tests – depending on which organism(s) are suspected
Other CSF tests for infectious diseases that are less commonly ordered include:
- CSF AFB smear and culture may be positive with tuberculosis and with other mycobacteria
- CSF molecular tests for Mycobacteria tuberculosis when tuberculosis is suspected
- CSF syphilis testing (VDRL) positive with neurosyphilis (involvement of the brain by syphilis); a negative does not rule out brain involvement
Normal CSF has no or very few cells present and appears clear. If the CSF sample appears clear, a small drop of undiluted CSF is examined under a microscope, and cells are counted manually. If the number of cells present are very few (for example, 5 or less), the laboratory may or may not perform a cell differential (see below). If cells are numerous (such as greater than 5), a differential will most likely be done. To perform a differential, labs will often use a special centrifuge(cytocentrifuge) to concentrate the cells at the bottom of a test tube. A sample of the concentrated cells is placed on a slide, treated with special stain, and an evaluation of the different kinds of WBCs present is performed.
However, if the CSF is very cloudy or bloody, which can indicate the presence of many cells, the specimen may be run on an automated cell counter for cell enumeration. These samples may be cytocentrifuged, but if there are too many cells present in the centrifuged sample, an accurate differential may be difficult to perform. In those cases, the specimen may be diluted, cytocentrifuged, and then stained.
If cancer is suspected or has been previously diagnosed, the sample is usually cytocentrifuged regardless of the number of cells counted, and a differential is performed.
- CSF total cell counts
- Red blood cell (RBC) count. Normally no red blood cells are present in the CSF. The presence of red blood cells may indicate bleeding into the CSF or may indicate a “traumatic tap” - blood that leaked into the CSF sample during collection.
- White blood cell (WBC) count. Normally less than 5 cells are present in the adult. A significant increase in white blood cells in the CSF is seen with infection or inflammation of the CNS.
- CSF WBC differential
Small numbers of lymphocytes, monocytes (and, in neonates, neutrophils) are normal in a sample of CSF. There may be:
- an increase in neutrophils with a bacterial infection
- an increase in lymphocytes with a viral infection
- sometimes an increase in eosinophils with a parasitic infection
- abnormal and increased numbers of WBCs may be seen with leukemia that is present in the CNS
- abnormal cells may be present with cancerous tumors
- immune disorders of the CSF, such as multiple sclerosis, may also cause a slight increase in lymphocytes.
There may be an increase in the different types of WBCs with a variety of other conditions, including brain abcess, following seizures or bleeding within the brain or skull, metastatic tumor, Guillain-Barré syndrome, and inflammatory disorders such as sarcoidosis.
- CSF cytology – a cytocentrifuged sample is treated with a special stain and examined under a microscope for abnormal cells. This is often done when a CNS tumor or metastatic cancer is suspected. The presence of certain abnormal cells, such as tumor cells or immature blood cells, can indicate what type of cancer is involved.
- CSF total cell counts
Exames relacionados: Glucose, Total Protein, CBC (Complete Blood Count), Lactate, Protein Electrophoresis, Antibody Tests, AFB Smear and Culture, Blood Culture, Herpes, Lyme Disease, Rubella, Syphilis, West Nile Virus
Em outros sites da Internet
American Family Physician: Cerebrospinal Fluid Analysis
MedlinePlus Medical Encyclopedia: CSF chemistry
MedlinePlus Medical Encyclopedia: Cerebral spinal fluid (CSF) collection
EMedicine: Lumbar Puncture
Journal of the American Medical Association: Lumbar Puncture
National Institute of Neurological Disorders and Stroke (NINDS): Meningitis and Encephalitis Fact Sheet