Cerebrospinal Fluid (CSF) Analysis
When your healthcare provider suspects that your symptoms are due to a condition or disease involving your central nervous system
You will be instructed to empty your bladder and bowels prior to sample collection. It will be necessary to lie still in a curled-up fetal position during the collection and to lie flat and still for a time period after the collection.
Cerebrospinal fluid (CSF) is a clear, watery liquid that flows around the brain and spinal cord, surrounding and protecting them. A CSF analysis is a group of tests that evaluate substances in CSF in order to diagnose conditions affecting the brain and spinal cord (central nervous system).
CSF is formed and secreted by the choroid plexus, a special tissue that has many blood vessels and that lines the small cavities or chambers (ventricles) in the brain. It is continually produced, circulated, and then absorbed into the blood. About 17 ounces (500 mL) are 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 the bloodstream 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.
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 central nervous system conditions.
- Infections and inflammation in the meninges, the layers of tissue that surround the spinal cord and brain, can disrupt the blood-brain barrier and allow white blood cells (WBCs) and red blood cells (RBCs) and increased amounts of protein into the CSF. Meningitis, an infection in the meninges, and encephalitis, an infection in the brain, can also lead to the production of antibodies, which can be detected in the CSF.
- Autoimmune diseases that affect the central nervous system, 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 white blood cells in the CSF and cancerous tumors can result in the presence of abnormal cells.
- Alzheimer disease is an irreversible form of dementia. Measuring amyloid beta 42 (Aß42) and tau protein in CSF may help establish a diagnosis for this disease.
These changes from normal CSF constituents make the examination of cerebrospinal fluid valuable as a diagnostic tool.
For more on CSF tests, see the "How is it used?" section.
How is the sample collected for testing?
A sample of cerebrospinal fluid (CSF) is collected by a health practitioner 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 person being tested 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 collection and to lie flat and still 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 brain and spinal cord (central nervous system). They may be divided into four main categories:
- Infectious diseases such as meningitis and encephalitis—testing is used to determine if infection is caused by bacteria, viruses or, less commonly, by Mycobacterium tuberculosis, fungi or parasites, and to distinguish them 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
- Autoimmune disorders, such as Guillain-Barré syndrome, sarcoidosis or multiple sclerosis
- Tumors located within the central nervous system (primary) or that spread to the central nervous system (metastatic cancer)
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 (total number of cells present)
- CSF differential cell count (numbers of different types of cells present)
- 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 a person has and the disease the health practitioner suspects may be 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. Many of the substances in CSF are also in blood and the relative amounts in CSF and blood are often compared. Normally, levels of certain constituents of CSF, such as protein and glucose, are reflective of their concentration in the blood.
- 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.
See below for details on these tests.
When is it ordered?
CSF analysis may be ordered when a health practitioner suspects that a person has a condition or disease involving their central nervous system. A person's medical history may prompt the request for CSF analysis. It may be ordered when someone has suffered trauma to the brain or spinal cord, has been diagnosed with cancer that may have spread into the central nervous system, or has signs or symptoms suggestive of central nervous system involvement.
The signs and symptoms of central nervous system 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 central nervous system bleeding or infection, or may be slow to develop, indicating a chronic disease, such as multiple sclerosis or Alzheimer disease.
Depending on a person's history, a healthcare provider may order CSF analysis when some combination of the following signs and symptoms appear, especially when accompanied by flu-like symptoms that intensify over a few hours to a few days and fever:
- Changes in mental status and consciousness
- Sudden, severe or persistent headache or a stiff neck
- Confusion, hallucinations or seizures
- Muscle weakness or lethargy, fatigue
- Nausea (severe or prolonged)
- 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.
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 test results may mean, see the sections below on:
- CSF physical characteristics
- CSF chemical tests
- CSF microscopic examination
- CSF infectious disease tests
Is there anything else I should know?
Bacterial and parasitic (such as amebic) meningitis are medical emergencies. A healthcare provider must rapidly distinguish between these conditions, viral meningitis, which is typically milder, and other conditions with similar symptoms. Because prompt treatment is crucial, the health practitioner may start the person affected on a broad-spectrum antibiotic before the diagnosis has been definitely determined.
To help diagnose a central nervous system-related illness, a healthcare provider may want to know about recent vaccinations, sickness, contact with others who are ill, places a person has traveled to, what symptoms a person is experiencing, and their duration.
What is a lumbar puncture (spinal tap) and how is it performed?
The lumbar puncture 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 important 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. An "opening" or initial pressure reading of the CSF is obtained. The health practitioner 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 headache.
The lumbar puncture procedure usually takes less than half an hour. For most patients, it is a moderately uncomfortable procedure. The most common sensation is a feeling of pressure when the needle is introduced. Let your healthcare provider 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. 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.
Are there other reasons to do a lumbar puncture?
Yes. Sometimes it will be performed to introduce anesthetics or medications into the CSF. Repeated punctures are sometimes used to decrease CSF pressure.
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 central nervous system 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 tests that may be ordered along with or following CSF testing include:
• 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
• CBC (complete blood count) to evaluate cell counts in blood
• Antibodies for a variety of viruses, such as West Nile Virus
• CMP (comprehensive metabolic panel), a group of tests used to evaluate electrolyte balance and organ function
Physical Characteristics (pressure and appearance)
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 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 lumbar puncture site or sinus fracture).
The appearance of the sample of CSF is usually compared to a sample of water.
- 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 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 people with certain types of cancers or meningitis.
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(white blood cells) 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 healthcare practitioner 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; the level is usually increased with bacterial meningitis and not with viral meningitis; may also be elevated with leukemia or stroke.
- CSF glutamine — may be increased with liver disease, hepatic encephalopathy or 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).
- Amyloid beta 42 (Aß42) and tau protein—used in the evaluation of Alzheimer disease. In a symptomatic person, a low Aß42 CSF level along with a high tau level reflects an increased likelihood of Alzheimer disease.
Normal CSF has no or very few cells present and appears clear. A small drop of CSF is examined under a microscope, and cells are counted manually. If the number of cells present is very few (for example, 5 or less in an adult), 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 white blood cells present is performed.
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 central nervous system.
- CSF white blood cell (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 or fungal 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 central nervous system
- although they may not be WBCs, abnormal cells from cancerous tumors may be present; if they are seen on a differential, CSF cytology will be performed (see below).
- a slight increase in lymphocytes may be seen with immune disorders of the central nervous system, such as multiple sclerosis.
There may be an increase in the different types of WBCs with a variety of other conditions, including brain abscess, following seizures or bleeding within the brain or skull, metastatic tumor, 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 central nervous system 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
Tests for Infections
- CSF gram stain for direct observation of microorganisms under a microscope. A sample of CSF is centrifuged and the concentrated portion is placed on a slide and treated with a special stain for examination under the microscope. If bacteria or fungi are present on a CSF gram stain, then the patient probably has bacterial or fungal meningitis.
- 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 affected person and prophylaxis (preventive treatment) 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 health practitioner strongly suspects a central nervous system infection, then additional testing may be ordered. This may include one or more of the following:
- Detection of viruses – there are multiple ways to detect viruses in CSF. Most commonly, polymerase chain reaction (PCR) testing is used to detect viral genetic material (DNA, RNA) but viral antigen tests and cultures may also be used.
- CSF Cryptococcal antigen – in addition to culture, this test may be done to detect a fungal infection caused by the yeast Cryptococcus neoformans.
- 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 testing may be positive with Mycobacterium tuberculosis and with other mycobacteria. Molecular tests specific for Mycobacteria tuberculosis may be performed when tuberculosis is suspected.
- Parasites may also be detected in CSF with laboratory tests such as molecular tests or culture. Parasitic meningitis or encephalitis are rare and can be lethal. One example is an infection caused by the free-living amoeba, Naegleria fowleri, a single-cell parasite that can be found in warm water lakes and rivers. Infection occurs when the parasite enters the respiratory system through the nose of a person swimming in contaminated water.
- CSF syphilis testing (VDRL) may be positive with neurosyphilis, infection of the brain by syphilis; a negative result does not necessarily rule out brain involvement.