Predictors for Therapy Response to Intrathecal Corticosteroid Therapy in Multiple Sclerosis.

Katja Vohl,Barbara Gisevius,Aiden Haghikia,Alexander Duscha,Johannes Kaisler,Ralf Gold

doi:10.3389/fneur.2019.00132

Katja Vohl, Barbara Gisevius + Show 4 more

Open Access

https://doi.org/10.3389/fneur.2019.00132

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Abstract

Objective: The autoimmune disease Multiple Sclerosis (MS) represents a heterogeneous disease pattern with an individual course that may lead to permanent disability. In addition to immuno-modulating therapies patients benefit from symptomatic approaches like intrathecal corticosteroid therapy (ICT), which is frequently applied in a growing number of centers in Germany. ICT reduces spasticity, which elongates patient's walking distance and speed, thus improves quality of life.Methods: In our study we set out to investigate cerebrospinal fluid (CSF) parameters and clinical predictors for response to ICT. Therefore, we analyzed 811 CSF samples collected from 354 patients over a time period of 12 years. Patients who received ICT were divided in two groups (improving or active group) depending on their EDSS-progress. As control groups we analyzed data of ICT naïve patients, who were divided in the two groups as well. Additionally we observed the clinical progress after receiving ICT by comparison of patients in both groups.Results: The results showed clinical data had a significant influence on the probability to benefit from ICT. The probability (shown by Odds Ratio of 1.77–2.43) to belong to the improving group in contrast to the active group is significantly (p < 0.0001) higher at later stages of disease with early disease onset (< 35 years, OR = 2.43) and higher EDSS at timepoint of ICT-initiation (EDSS > 6, OR = 2.06). Additionally, we observed lower CSF cell counts (6.68 ± 1.37 μl) and lower total CSF protein (412 ± 18.25 mg/l) of patients who responded to ICT compared to patients who did not (p < 0.05). In the control group no significant differences were revealed. Furthermore analyses of our data revealed patients belonging to the improving group reach an EDSS of 6 after ICT-initiation less often than patients of the active group (after 13 years 39.8% in the improving group, 67.8% in the active group).Conclusion: Our study implies two relevant messages: (i) although the study was not designed to prospectively assess clinical data, in this cohort no severe side effects were observed under ICT; (ii) disease onset, EDSS, CSF cell count, and total protein may serve as predictive markers for therapy response.

Highlights

Multiple Sclerosis (MS) is one of the most common nontraumatic neurological diseases of young adults [1]
With this study we addressed the following questions: (I) Are there any differences in standard cerebrospinal fluid (CSF) parameters to distinguish between response and non-response to intrathecal corticosteroid therapy (ICT)?; and (II) which clinical parameters indicate a beneficial response to ICT?
The amount of total protein in the CSF was significantly lower in the improving group (p = 0.0014, improving group 412 ± 18.25 mg/l vs. active group 462.4 ± 14.04 mg/l; Figure 1C)

Summary

Introduction

Multiple Sclerosis (MS) is one of the most common nontraumatic neurological diseases of young adults [1]. After insufficient response to first-line (oral) antispastic therapies, intrathecal corticosteroid therapy (ICT) is an adjuvant option to reduce permanent disability [3]. Several studies have previously shown the efficacy of ICT in various cohorts [3, 4]. ICT improves effectively neuropathic pain which is caused by disease activity [5]. ICT is stated as a safe and effective option for the reduction of disability [6]. ICT has a beneficial impact on bladder function [3] and generally improves quality of life in responsive patients. ICT is a promising option to slow down disease progression and reduce permanent disability. The aim of our study was to identify possible CSF markers that may predict the individual response to ICT. CSF, due to its proximity to MS pathomechanism, has been shown to be a suitable biocompartment, e.g., for epigenetic markers [7], that is usually not affected by systemic metabolic processes derived from the peripheral blood [8]

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