Changes in vitamin B12 and tumour necrosis factor-a levels in cerebrospinal fluid of patients with different subtypes of multiple sclerosis

Objectives: There has long been considerable debate concerning the possible role of tumour necrosis factor (TNF)-α and vitamin B 12 (cobalamin, Cbl) in the pathogenesis of multiple sclerosis (MS). We have previously demonstrated experimentally (in Cbl-deficient rats) and clinically (in patients with pernicious anaemia or subacute combined degeneration) that Cbl deficiency induces an imbalance in the levels of TNF-α and epidermal growth factor in the central nervous system (CNS) and biological fluids serum and cerebrospinal fluid (CSF)) by increasing the former and decreasing the latter. Furthermore, these abnormalities are normalised by Cbl replacement treatment. All of these results indicate that Cbl has new noncoenzymatic functions insofar as it seems to modulate the synthesis of some cytokines and/or growth factors in the CNS (and probably elsewhere) and their levels in some biological fluids of mammals. The aims of this ongoing study are: (a) to determine the levels of Cbl and TNF-α in the CSF of MS patients stratified on the basis of their MS subtype; and (b) to verify the correlation between them in order to clarify whether Cbl maintains its physiological regulatory role on CSF TNF-α levels. Methods: CSF samples are being collected from patients with primaryprogressive (PP), relapsing-remitting (RR), or secondary-progressive (SP) and assayed for Cbl and TNF-α levels. The Cbl levels are determined by means of a radioassay, and the TNF-α levels by means of an enzyme-linked immunosorbent assay kit.A control group consists of patients with non-immunological and non-neoplastic neurological diseases. Results: The preliminary results so far indicate that the RR-MS and SPMS patients have statistically significantly higher Cbl levels than those of the PP-MS and control patients. The RR-MS and SP-MS patients have significantly lower TNF-α levels than the PP-MS and control patients,with the levels being higher in the RR-MS than the SP-MS patients. The negative correlation between Cbl and TNF-α levels is statistically significant. Conclusion: Given the clear-cut difference in the CSF Cbl and TNF-α levels between PP-MS patients and RR- or SP-MS patients, our results support the notion that PP-MS may be a very different disease as compared to RRMS. The pathological significance of these differences merits further investigation.