What is CSF protein electrophoresis test? 

A CSF protein electrophoresis test determines the different types of proteins present in your cerebrospinal fluid (CSF). CSF is a clear liquid in the brain and the spinal cord. It functions as a cushion and shock absorber for the brain and also nourishes and detoxifies the brain.

Normally, very little protein is found in the brain because proteins are large molecules that cannot cross the blood-brain barrier (BBB) - a layer separating the blood from the CSF. However, in certain inflammatory or immune disorders, the BBB is damaged and proteins leak into the CSF.

The CSF protein electrophoresis test uses an electric current to separate the proteins in the CSF sample into a pattern of bands. The thickness of the band will then determine the amount of the protein. The following are the various proteins that are detected in the protein electrophoresis test:

  • Prealbumin and albumin 
  • Globulins: These are subdivided into alpha1, alpha2, beta and gamma. Most gamma globulins are immunoglobulins (antibodies). 
    • Immunoglobulins (Ig) are protective proteins produced by our body to destroy bacteria, viruses or any harmful foreign bodies. The most common immunoglobulin is IgG.
    • Oligoclonal bands are abnormal immunoglobulins seen as distinct bands in the CSF. It is detected in inflammatory or immune conditions of the brain, especially multiple sclerosis.
  1. Why is CSF Protein Electrophoresis test performed?
  2. How do you prepare for a CSF Protein Electrophoresis test?
  3. How is a CSF Protein Electrophoresis test performed?
  4. CSF Protein Electrophoresis test results and normal values

Your healthcare practitioner may order a CSF protein electrophoresis test primarily to check for multiple sclerosis.

Multiple sclerosis is an autoimmune disorder in which our body mistakenly produces antibodies that destroy the protective covering around the brain cells. The symptoms of multiple sclerosis are:

  • Numbness, tingling or pain
  • Fatigue
  • Disturbances in vision
  • Muscle symptoms:
    • Loss of balance
    • Weakness 
    • Difficulty walking
    • Tremors 
    • Speech defects
    • Problems with bowel and bladder control
  • Psychological symptoms:

This test can also be ordered to check for:

  • Inflammatory conditions of the central nervous system (CNS), such as meningitis, encephalitis and myelitis 
  • Certain tumours which may secrete proteins into the CSF
  • Bacterial and viral infections affecting the CNS

No preparation is needed before this test. You may be instructed to empty your bladder and bowels before the test. If you have recently undergone myelography (an imaging test of the spinal cord), inform your doctor before the test. Discuss with your doctor about any prescribed, non-prescribed or illicit medicines, vitamins or supplements you may be taking.

For this test, your healthcare practitioner will draw a CSF sample by a method called a spinal tap or lumbar puncture. He/she will explain to you the steps of this test before it is conducted. Here is the procedure for the spinal tap:

  • Your healthcare practitioner will ask you to sit or lie on your side on an examination table. You must remain still during the procedure, as movement can cause injury.
  • The doctor will clean your back using an antiseptic solution and numb the area by injecting an anaesthetic into your skin.
  • When the area becomes numb, he/she will insert a thin, hollow needle between two bones of your lower spine. 
  • A small amount of CSF will be collected and sent to the laboratory for analysis.
  • After the procedure, you may be asked to lie on your back for at least an hour to avoid having a headache later.

A few risks associated with the test are:

Normal results:

The following table shows the normal levels of various proteins in the CSF:

Total protein  15-45 mg/dL (milligrams per decilitre) 
Pre-albumin 0.0-3.1 mg/dL (2%-7%) 
Albumin 8.4-34.2 mg/dL (56%-76%) 
Alpha1 globulin  0.0-3.1 mg/dL (2%-7%)
Alpha2 globulin  0.0-5.4 mg/dL (4%-12%)
Beta globulin  0.0-8.1 mg/dL (8%-18%)
Gamma globulin  0.0-5.4 mg/dL (3%-12%)
Oligoclonal bands  None 
IgG 0.0-4.5 mg/dL
IgG index  0.3-0.8
IgG-to-albumin ratio 0.09-0.25
IgG synthesis rate  0.0-8.0 mg/day 

These reference ranges may vary slightly from one laboratory to another. Please speak to your doctor for an accurate interpretation of your results.

Abnormal results:

The following conditions are associated with increased protein levels in the CSF:

  • Increase in the CSF IgG or IgG-to-albumin index is seen in:

    • Multiple sclerosis
    • Tumours of the brain and meninges
    • Subacute sclerosing panencephalitis (SSPE) (a neurological disease characterized by inflammation of the brain)
    • Prolonged CNS infections
    • Meningitis, Guillain-Barré syndrome (an autoimmune condition in which the immune system attacks the peripheral nerves) and lupus erythematosus (a long term condition which affects the cartilage and the lining of the blood vessels that give flexibility and strength to the structure of our body)
  • Increase in the CSF albumin index is seen in:
    • Obstruction of CSF circulation
    • Systemic lupus erythematosus of the CNS
    • Guillain-Barré syndrome
    • Polyneuropathy
    • Cervical spondylosis
    • Damage to the BBB
    • Diabetes mellitus
  • Increased CSF gamma-globulin along with the presence of oligoclonal bands occurs in:
    • Multiple sclerosis 
    • Neurosyphilis
    • Progressive rubella panencephalitis (a condition similar to SSPE caused due to a rubella virus)
    • Subacute sclerosing panencephalitis
    • Cerebral infarction
    • Viral and bacterial meningitis
    • Cryptococcal meningitis
    • Idiopathic polyneuritis
    • Burkitt's lymphoma (a type of cancer which starts from the B immune cell)
    • HIV-I (acquired immunodeficiency syndrome [AIDS])
    • Guillain-Barré syndrome
  • Increased CSF synthesis of IgG occurs in:
    • Multiple sclerosis
    • Inflammatory neurologic diseases
    • Post-polio syndrome

Disclaimer: All results must be clinically correlated with the patient’s complaints to make a complete and accurate diagnosis. The above information is provided from a purely educational point of view and is in no way a substitute for medical advice by a qualified doctor.

References

  1. National Multiple Sclerosis Society [Internet]. New York (U.S.A.); Cerebrospinal Fluid (CSF)
  2. University of Rochester Medical Center [Internet]. Rochester (NY): University of Rochester Medical Center; Immunofixation and Protein Electrophoresis (CSF)
  3. MedlinePlus Medical Encyclopedia: US National Library of Medicine; [link]
  4. MedlinePlus Medical Encyclopedia: US National Library of Medicine; Urine protein electrophoresis test
  5. ARUP Labs [Internet]. University of Utah. Plasma Cell Dyscrasias
  6. Pagana KD, Pagana TJ, Pagana TN. Mosby’s Diagnostic and Laboratory Test Reference. 14th ed. Pg: 576,578
  7. Lechner-Scott J, et al. The frequency of CSF oligoclonal banding in multiple sclerosis increases with latitude. Mult Scler. 2012 Jul;18(7):974-82. PMID: 22185806.
  8. Goldman L, Schafer AI, eds. Goldman-Cecil Medicine. 25th ed. Philadelphia, PA: Elsevier Saunders; 2016:chap 396,411.
  9. Daroff RB, Jankovic J, Mazziotta JC, Pomeroy SL, eds. Bradley's Neurology in Clinical Practice. 7th ed. Philadelphia, PA: Elsevier; 2016:chap 80,95.
  10. Heine M, van de Port I, Rietberg MB, van Wegen EE, Kwakkel G. Exercise therapy for fatigue in multiple sclerosis. Cochrane Database Syst Rev. 2015;(9):CD009956. PMID: 26358158
  11. Saguil A, Kane S, Farnell E. Multiple sclerosis: a primary care perspective. Am Fam Physician. 2014 Nov 1;90(9):644-652. PMID: 25368924.
  12. Fischbach FT. A Manual of Laboratory and Diagnostic Tests. 7th ed. 2003. Lippincott Williams & Wilkins Publishers. Pp: 208
  13. MedlinePlus Medical Encyclopedia: US National Library of Medicine; Cerebrospinal Fluid (CSF) Analysis
  14. UN Medical Center: UNC Health Care [Internet]. University of Nebraska. Chapel hill (NE), U.S.; CSF Protein Electrophoresis w/Ratio
  15. National Organisation of Rare Disorders [Internet]. Danbury, CT, U.S. Subacute Sclerosing Panencephalitis
  16. World Health Organization [Internet]. Geneva (SUI): World Health Organization; Guillain–Barré syndrome
  17. Merck Manual Professional Version [Internet]. Kenilworth (NJ): Merck & Co. Inc.; c2019. Non-Hodgkin Lymphomas
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