Effects on cerebrospinal fluid biomarkers in multiple sclerosis patients after repeated intrathecal triamcinolone acetonid application

Objective: This pilot study wanted to characterize the effects on cerebrospinal fluid (CSF) Tau protein, S-100, interleukin (IL) -6-type cytokine, beta-trace protein (beta-trace) and beta-2 microglobulin (beta 2MG) induced by repeated intrathecal triamcinolone acetonid (TCA) applications in multiple sclerosis patients.

Methods: In this prospective pilot study 10 patients suffering from Multiple Sclerosis(MS) (4 relapsing remitting [RR], 6 secondary or primary progressive [SP/PP]) were included. Three TCA applications were performed as part of an ongoing trial every second day to reduce spasticity.

Results: The median EDSS was 5.5 (range 1–8) at baseline and 4.5 (1–8) at follow up. The mean CSF IL-6 levels were 3.14 pg/ml at baseline (normal range <24 pg/ml) and at time 2 (40.75 pg/ml) and at time 3 (3.83 pg/ml). The mean CSF beta-trace levels were 18.95mg/l at baseline (normal range 15–36mg/l), at visit 2 (18.23mg/l) and visit 3 (18.95mg/l). The mean CSF beta 2MG levels were 1.27mg/l at baseline (normal range 0.8–2.0mg/l), at visit 2 (1.24mg/l) and visit 3 (1.15mg/l). The mean CSF Tau protein levels were 196.1 pg/ml at baseline (age dependent normal range 75–274 pg/ml), 243.9 pg/ml at visit 2 and 272.3 pg/ml at visit 3. The mean CSF S-100 levels were 1.24ng/ml at baseline, 1.13ng/ml at visit 2 and 1.06ng/ml at visit 3. We observed a significant increase of Tau protein levels over the observation period for all patients from baseline to visit 3. Correcting for repeated measurements there was no change of the other measured CSF biomarker levels over the observation period.

Conclusion: This pilot study demonstrated that an increase of CSF-Tau protein occurs consistently in MS patients with intrathecal TCA applications. The degree of alteration may be influenced by the MS subtype. Our ongoing treatment trial or further studies on larger cohorts of patients have to evaluate whether these markers may serve as surrogate marker for treatment response and/or disease activity.