Cerebrospinal fluid in multiple sclerosis

In patients with multiple sclerosis, a qualitative cytological examination should always be carried out. Besides the finding of plasmocytic forms, which are considered to be one of the proofs of intrathecal synthesis of immunoglobulins, this examination also provides invaluable information concerning the reaction of the monocyte-macrophage system in the CSF compartment. It should be noted on the scope of biochemical examinations of cerebrospinal fluid in multiple sclerosis that it is most important to return to the simple and inexpensive method. 

Spence, A. M., Immunoglobulins in cerebrospinal fluid in multiple sclerosis. Hurru Pathol. 14, 99-103 (1983). 

Stourac, R, Differential diagnostic relevance of the blood-CSE barrier function and oligoclonal IgG synthesis in cerebrospinal fluid in multiple sclerosis. Clin. Biochem. Metab. 6(27), 210-212 (1998). 

Walsh MJ, TourteUotte WW. The cerebrospinal fluid in multiple sclerosis. In Hallpike JF, Adams CWM, TourteUotte WW, editors. Multiple sclerosis. London Chapman Hall, 1983 275-358. 

Tourtellotte, W. W., The cerebrospinal fluid in multiple sclerosis, in Handbook of Clinical Neurology, Koetsier, J. C., Ed., Elsevier, Amsterdam, 1985, chap. 3. 

Rotteveel, F. T. M., Kuenen, B., Kokkelink, I., Meager, A., and Lucas, C. J., Relative increase of inflammatory CD4+ T cells in the cerebrospinal fluid of multiple sclerosis patients and control individuals, Clin. Exp. Immunol., 79, 15, 1990. 

In multiple sclerosis, which is a demyelinating disease, there is loss of both phospholipids (particularly ethanolamine plasmalogen) and of sphingolipids from white matter. Thus, the lipid composition of white matter resembles that of gray matter. The cerebrospinal fluid shows raised phospholipid levels. 

The concentration of total protein increases slightly with age. In multiple sclerosis, we have not proved any dependence of the level of total protein in cerebrospinal fluid on other clinical parameters. 

Concentration of total protein in cerebrospinal fiuid is the essential biochemical parameter. It is tme that the concentration of total protein in cerebrospinal fluid varies with a mild to significant increase with regard to the reference range. It is well known that the concentration of total protein in cerebrospinal fluid exceeding 1 g L means a principal challenge to the diagnosis of multiple sclerosis. In multiple sclerosis, the levels of total protein are either normal or only insignificantly... 

Chiodi, R, Sundqvist, V. A., Link, H., and Norrby, E., Viral IgM antibodies in serum and cerebrospinal fluid in patients with multiple sclerosis and controls. Acta Neurol. Scand. 75(3), 201-208 (1987). 

H2. Havrdova, E., Racek, P., and JedUcka, R, Relation of intrathecal synthesis of IgG including IgG subclasses to cytokine levels in cerebrospinal fluid in patients with multiple sclerosis. Clin. 

R6. Reiber, H., Cerebrospinal fluid analysis. In CSF Analysis in Multiple Sclerosis (E. J. Thomson, M. Trojano, and R Livrea, eds.). Springer-Verlag, Milano, 1996. 

Cerebrospinal Fluid Analysis in Multiple Sclerosis Francisco A. Luque and Stephen L. Jaffe... 

Noben IP, Dumont D, Kwasnikowska N, Verhaert P, Somers V, et al. Lumbar cerebrospinal fluid proteome in multiple sclerosis characterization by ultraflltration, liquid chromatography, and mass spectrometry. J. Proteome Res. 2006 5 1647-1657. 

Determinations of antigen by the quantitative precipitin method were used routinely for many years in some institutions for the estimation of IgG in human cerebrospinal fluid, increases in cerebrospinal fluid IgG being found in multiple sclerosis and in neurosyphilis.In recent... 

Navikas V, Matusevicius D, Soderstrom M, et al. Increased interleukin-6 mRNA expression in blood and cerebrospinal fluid mononuclear cells in multiple sclerosis. J Neurolmmuno 1996 64 63-9. 

Svenningsson, A., Hansson, G. K., Andersen, O., Andersson, R., Patarroyo, M., and Sten, S., Adhesion molecule expression on cerebrospinal fluid T lymphocytes evidence for common recruitment mechanisms in multiple sclerosis, aseptic meningitis, and normal controls, Ann. Neurol., 34, 155, 1993. 

P7. Plum, C. M., and Hansen, S. E., Studies on variations in serum copper and serum copper oxidase activity together with studies on the copper content of the cerebrospinal fluid, with particular reference to the variations in multiple sclerosis. Acta Psychiat. Neurol. Scand. 36, Suppl. 148, 41-78 (1960). 

Lassman H, Suchanek G, Ozawa K. Histopathology and the blood-cerebrospinal fluid barrier in multiple sclerosis. Ann Neurol 1994 36 S42-S46. 

Frequin, S. T., Barkhof, F.. lutmers, K, J and Hommes, O. R. (1992). The effects of high-dose mcthylprednisolone on gadolinium-cnhanccd magtictic rc.sonancc imaging and cerebrospinal fluid measurements in multiple sclerosis. J. Neiifoimmunol. 40, 265-272. 

The main clinical significance of cerebrospinal fluid (CSF) protein eleetrophoresis is for the detection of the oligoclonal bands, which are present in multiple sclerosis in the gamma region. Similar to urine, proteins in the CSF are present fluid in very low concentration (100 times less than serum). For the majority of the samples, a 10- to 20-fold concentration is preferred before analysis by CE (by the same membrane concentrators used for urine). CSF protein separation can be accomplished in less than 10 min with CE versus 2 h for AG with the ability to detect oligoclonal banding by this technique [36]. 

R41 N. W. Lutz and P. J. Cozzone, Metabolic Profiling in Multiple Sclerosis and Other Disorders by Quantitative Analysis of Cerebrospinal Fluid Using Nuclear Magnetic Resonance Spectroscopy , Curr. Pharm. Biotechnol., 2011, 12, 1016. 

The most characteristic abnormality in patients with multiple sclerosis is certainly the intrathecal synthesis of IgG. It can be demonstrated—with different sensitivity— by various methods, which can be divided into qualitative and quantitative methods. The gold standard for the demonstration of intrathecal synthesis of IgG is the detection of oligoclonal bands, which are not present in CSF, in the appropriately diluted serum (i.e., to the same concentration of IgG) by isoelectric focusing. This is a qualitative method and the description of its different modifications and interpretations goes beyond the scope of this chapter. This method is by far the most sensitive, and its sensitivity is reported between 90 and 100%. Here it is suitable to repeat that the detection of plasmocytic forms in cerebrospinal fluid may also be regarded as qualitative proof of intrathecal synthesis of immunoglobulins— although in this case the proof is obviously not specific for IgG from the theoretical point of view. 

Glucocorticoids given intrathecally can cause a rise in cerebrospinal fluid protein and carry the risk of arachnoiditis (SED-8, 820). Chemical meningitis has been reported after two intrathecal injections of methylpredni-solone acetate (450) and after lumbar facet joint block (SEDA-17, 450). Intraspinal injections of hydrocortisone for multiple sclerosis apparently led in one case to a cauda equina syndrome, with subsequent ulceromutilating acro-pathy (SEDA-17, 450). Intra-discal injections of triamcinolone acetonide in a number of French cases led to disk or epidural calcification, sometimes symptomless (SEDA-17, 450). 

M19. Misu, T., Onodera, H., Fujihara, K., Matsushima, K., Yoshie, O., Okita, N., Takase, S., and Itoyama, Y., Chemokine receptor expression on T cells in blood and cerebrospinal fluid at relapse and remission of multiple sclerosis Imbalance of Thl/Th2-associated chemokine signaling. J. Neuroimmunol. 114, 207-212 (2001). 

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