Medical Analysis

Comprehensive Medical Analysis of Cerebrospinal Fluid Examination Part – 6: Advanced Diagnostics, Rhinorrhoea, Otorrhoea, and Protein Electrophoresis

Introduction to Cerebrospinal Fluid Examination and Clinical Significance

Cerebrospinal Fluid Examination is an extensive and clinically significant topic. Its proper understanding is crucial, as the findings profoundly influence both diagnosis and prognosis, directly impacting patient care and clinical decision-making. Due to the vastness of this subject, it is not feasible to cover every aspect within a single presentation. This presentation is one of a series of six on Cerebrospinal Fluid Examination. Viewers are encouraged to go through the remaining five presentations for a complete and comprehensive understanding of this topic.

Special Investigations in Cerebrospinal Fluid: Protein Electrophoresis and Biomarkers

Special investigations in cerebrospinal fluid include protein electrophoresis and the measurement of albumin and immunoglobulin IgG [2, 14]. Protein electrophoresis of normal cerebrospinal fluid differs from normal serum by the presence of a prominent transthyretin band and an extra transferrin band called beta-2-transferrin or tau protein [2, 14]. Protein electrophoresis of cerebrospinal fluid is used for the identification of oligoclonal bands and to determine whether fluid submitted for examination is cerebrospinal fluid [1, 2, 4].

Identification of Oligoclonal Bands in Neurological Disorders

Concentrated cerebrospinal fluid is used for the detection of oligoclonal bands on agarose gel electrophoresis [1, 2]. These are two or more discrete bands in the gamma region [1, 2]. The presence of oligoclonal bands on cerebrospinal fluid protein electrophoresis that are absent on concurrently run serum protein electrophoresis is indicative of intrathecal synthesis of immunoglobulins [1, 7, 8]. Oligoclonal bands have been identified in the majority of patients (90 percent) with multiple sclerosis [1, 7, 8]. However, oligoclonal bands are not specific for multiple sclerosis and are seen in subacute sclerosing panencephalitis, neurosyphilis, viral central nervous system infections, and Guillain-Barre syndrome [1, 2, 7, 8].

Diagnostic Evaluation of Rhinorrhoea and Otorrhoea for Cerebrospinal Fluid Leakage

To determine whether fluid submitted for examination is cerebrospinal fluid, clear fluid leaking through the nose, known as rhinorrhoea, or through the ear, known as otorrhoea, after trauma or surgery is submitted for laboratory evaluation [4, 5, 6]. Due to the risk of recurrent meningitis, accurate identification of such fluid as cerebrospinal fluid is essential [4, 9, 10]. Protein electrophoresis of cerebrospinal fluid shows an extra transferrin band called tau protein, which is absent in other body fluids and secretions [4, 6, 9]. Tau protein is an enzymatically modified transferrin that moves just behind the unaltered transferrin in the beta region [4, 6, 14]. Identification of two isoform bands of transferrin on protein electrophoresis is a highly sensitive and specific test for the identification of fluid as cerebrospinal fluid, as other body fluids or secretions do not show the second isoform band [4, 6, 15].

Alternative and Historical Methods for Cerebrospinal Fluid Confirmation

In the old days when cerebrospinal fluid electrophoresis was not available, clinicians used to carry out sugar estimation of both the clear fluid running from the nose or ear along with blood sugar [11, 12]. If the fluid sugar is around 60 percent to that of blood sugar, the fluid submitted may be considered as cerebrospinal fluid by taking into account other clinical parameters [11, 12]. Nowadays, this method may still be practiced where immediate advanced laboratory facilities are not available [11, 12].

For Non-Medicos

What Is Cerebrospinal Fluid Testing?

Cerebrospinal fluid testing is an advanced medical laboratory procedure used to diagnose complex brain and spinal cord conditions [1, 3].

Why Test for Fluid Leaks from Nose or Ear?

Clear fluid leaking from the nose or ear following a head injury must be tested to see if it is brain fluid, preventing dangerous infections like meningitis [4, 9, 10].

Understanding Advanced Protein Testing Results

Special lab tests like protein electrophoresis identify unique protein markers, such as tau protein and oligoclonal bands, to diagnose conditions like multiple sclerosis or fluid leaks [1, 4, 7, 8].

References:

1. Link H. Oligoclonal immunoglobulin G in multiple sclerosis cerebrospinal fluid. Clin Exp Immunol. 1972;11(3):305–314.

2. Lowenthal A, Van Sande M, Karcher D. The electrophoretic pattern of gamma globulins in cerebrospinal fluid in multiple sclerosis and other diseases of the nervous system. J Neurochem. 1960;6(1):51–56. https://doi.org/10.1111/j.1471-4159.1960.tb13337.x

3. Kabat EA, Glusman M, Kilt BA. Quantitative estimation of the albumin and gamma globulin in normal and pathologic cerebrospinal fluid with special reference to multiple sclerosis. Am J Med. 1948;4(5):653–662. https://doi.org/10.1016/0002-9343(48)90388-8

4. Skedros DG, Cass SP, Brabham SE, Althaus S, Smith JK. Beta-2-transferrin assay in clinical management of cerebrospinal fluid rhinorrhea and otorrhea. J Otolaryngol. 1993;22(5):341–344.

5. Oberascher G. A valuable new clinical method for the diagnosis of cerebrospinal fluid fistulas. Rhinology. 1988;26(4):263–275.

6. Meurman OH, Irjala KY, Suonpää JT, Laurent BE. Beta-2-transferrin as a marker for cerebrospinal fluid leakage. Arch Otolaryngol Head Neck Surg. 1987;113(12):1323–1325. https://doi.org/10.1001/archotol.1987.01860120065023

7. Andersson M, Alvarez-Cermeño J, Bernardi G, Cogato I, Fredman P, Gallo P, et al. Cerebrospinal fluid in the diagnosis of multiple sclerosis: a consensus report. J Neurol Neurosurg Psychiatry. 1994;57(8):897–902. https://doi.org/10.1136/jnnp.57.8.897

8. Freedman MS, Thompson EJ, Deisenhammer F, Giovannoni G, Grimaldi Lm, Keir G, et al. Recommended and standardized protocol for CSF oligoclonal band evaluation in multiple sclerosis. Mult Scler. 2005;11(3):353–375. https://doi.org/10.1191/1352458505ms1151oa

9. Normolle D, Schlosser RJ, Harvey RJ, Oakley GM, Alt JA. Diagnosis of cerebrospinal fluid rhinorrhea: an evidence-based review with recommendations. Int Forum Allergy Rhinol. 2016;6(1):8–16. https://doi.org/10.1002/alr.21637

10. Mantur M, Lukaszewicz-Zajac M, Mroczko B, Szmitkowski M. Cerebrospinal fluid leakage–reliable diagnostic methods. Clin Chim Acta. 2011;412(11-12):837–840. https://doi.org/10.1016/j.cca.2011.02.019

11. Kirby MM, Kenan PD, Byington R. Cerebrospinal fluid rhinorrhea: diagnosis and management. Laryngoscope. 1999;109(2 Pt 1):277–281. https://doi.org/10.1097/00005537-199902000-00019

12. Cates JR, Scholp BH. Evaluation and management of cerebrospinal fluid rhinorrhea. Otolaryngol Clin North Am. 2011;44(5):1119–1135. https://doi.org/10.1016/j.otc.2011.06.012

13. Poser CM. The diagnosis of multiple sclerosis. Acta Neurol Scand Suppl. 1978;63:1–37.

14. Stibler H. Carbohydrate-deficient transferrin in serum: a new marker of potentially harmful alcohol consumption reviewed. Clin Chem. 1991;37(12):2029–2037.

15. Sloman AJ, Kelly RH. Transferrin allelic variants may cause false positives in the detection of cerebrospinal fluid fistulae. Clin Chem. 1993;39(7):1444–1445.

FAQ’s:

• What is cerebrospinal fluid testing?
  An advanced medical procedure used to diagnose complex brain and spinal cord conditions.
• Why test for fluid leaks?
  Clear fluid leaking from nose or ear must be tested to prevent dangerous meningitis infections.
• What does protein electrophoresis show?
  It reveals a prominent transthyretin band and an extra transferrin band called tau protein.
• What are oligoclonal bands?
  Discrete bands in gamma region indicating intrathecal synthesis of immunoglobulins during neurological disorders.
• Are oligoclonal bands specific?
  No, they appear in multiple sclerosis, neurosyphilis, viral infections, and Guillain-Barre syndrome.
• What is tau protein?
  An enzymatically modified transferrin moving behind unaltered transferrin in the beta region of electrophoresis.
• How is fluid leakage confirmed?
  Identification of two transferrin isoform bands serves as a highly sensitive and specific test.
• What is CSF rhinorrhoea?
  The leakage of clear cerebrospinal fluid through the nose following trauma or surgical procedures.
• What is CSF otorrhoea?
  The leakage of clear cerebrospinal fluid through the ear after experiencing trauma or surgery.
• What was the historical method?
  Clinicians compared fluid sugar to blood sugar levels when electrophoresis facilities were unavailable.

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