Effects of repeated intrathecal triamcinolone-acetonide application on cerebrospinal fluid biomarkers of axonal damage and glial activity in multiple sclerosis patients

Abstract

Background and objectives: Multiple sclerosis (MS) is the most common inflammatory disease of the central nervous system in young adults. Over time, the disease progresses and, with accumulating disability, symptoms such as spasticity may occur. Although several treatment options are available, some patients may not respond to first-line therapeutics. However, some of these patients may benefit from intrathecally administered triamcinolone-acetonide (TCA), a derivative of glucocorticosteroids (GCS). GCS may have neurotoxic effects, and cell apoptosis may occur. The aim of this study was to investigate the effects of TCA on biomarkers in the cerebrospinal fluid (CSF) suggestive of neurodegeneration.

Methods: In order to assess neurotoxic effects of TCA, neurofilament heavy-chain (NfH)(SMI35), tau protein, and S-100B protein levels were determined before and during treatment with TCA in 54 patients with primary progressive MS, as well as relapsing MS (relapsing-remitting and secondary progressive MS).

Results: NfH(SMI35) levels in the CSF of patients treated with TCA intrathecally did not increase significantly during the treatment cycle (p = 0.068). After application of TCA, tau protein levels were increased significantly at day 4 (p = 0.03) and at day 8 (p ≤ 0.001). S-100B protein levels decreased significantly (p ≤ 0.05) during treatment with TCA.

Conclusion: NfH(SMI35) levels did not change significantly; however, tau protein levels did increase significantly within the reference range. Taking these findings together, the long-term effects of TCA on NfH(SMI35) and tau protein levels need to be investigated further to understand whether levels of both biomarkers will change over repeated TCA applications. Interestingly, S-100B protein levels decreased significantly during the first applications, which may have represented reduced astrocytic activity during TCA treatment.

Fig. 1

Concentration of NfH^SMI35 during the first cycle of triamcinolone-acetonide (TCA) therapy. Statistical analysis: Friedman test, Wilcoxon test. NfH neurofilament heavy-chain

Fig. 2

Concentration of Tau protein during the first cycle of triamcinolone-acetonide (TCA) therapy. Statistical analysis: Friedman test, Wilcoxon test

Fig. 3

Concentration of S-100B protein during the first cycle of triamcinolone-acetonide (TCA) therapy. Statistical analysis: Friedman test, Wilcoxon test