Systemic Effects by Intrathecal Administration of Triamcinolone Acetonide in Patients With Multiple Sclerosis.

Andreas Hoeflich,Holger S Willenberg,Julia Brenmoehl,Manuela Bastian,Christina Walz,Ina Schröder,Martin Reincke,Armin Tuchscherer,Brit Fitzner,Michael Hecker,Uwe Klaus Zettl

doi:10.3389/fendo.2020.00574

Andreas Hoeflich, Holger S Willenberg + Show 9 more

Open Access

https://doi.org/10.3389/fendo.2020.00574

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Abstract

In patients suffering from multiple sclerosis (MS), intrathecal injection of triamcinolone acetonide (TCA) has been shown to improve symptoms of spasticity. Although repeated intrathecal injection of TCA has been used in a number of studies in late-stage MS patients with spinal cord involvement, no clinical-chemical data are available on the distribution of TCA in cerebrospinal fluid (CSF) or serum. Moreover, the effects of intrathecal TCA administration on the concentrations of endogenous steroids remain poorly understood. Therefore, we have quantified TCA and selected endogenous steroids in CSF and serum of TCA-treated MS patients suffering from spasticity. Concentrations of steroids were quantified by LC-MS, ELISA, or ECLIA and compared with the blood-brain barrier status, diagnosed with the Reibergram. The concentration of TCA in CSF significantly increased during each treatment cycle up to >5 μg/ml both in male and female patients (p < 0.001). Repeated TCA administration also evoked serum concentrations of TCA up to >30 ng/ml (p < 0.001) and severely depressed serum levels of cortisol and corticosterone (p < 0.001). In addition, concentrations of circulating estrogen were significantly suppressed (p < 0.001). Due to the potent suppressive effects of TCA on steroid hormone concentrations both in the brain and in the periphery, we recommend careful surveillance of adrenal function following repeated intrathecal TCA injections in MS patients.

Highlights

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) characterized by focal demyelinating lesions, axonal damage, and synaptic loss [1, 2]
An individual data set is provided by Supplementary Tables 1A,B. further containing the concentrations of steriods in serum and cerebrospinal fluid (CSF)
MS represents an unapproved indication for the application of triamcinolone acetonide (TCA) and, TCA is used off-label in selected MS patients with predominant spinal cord symptoms such as intractable spasticity [10,11,12,13,14]

Summary

Introduction

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) characterized by focal demyelinating lesions, axonal damage, and synaptic loss [1, 2]. Late-stage patients often show symptoms such as depression, fatigue, paresis, and spasticity. Spasticity severely impairs the patient’s abilities and is associated with pain and contractures [6]. Treatment options for the medical management of MS-related spasticity include oral application of baclofen (gamma-aminobutyric acid agonist), tizanidine (centrally acting α2 adrenergic agonist), dantrolene sodium (postsynaptic muscle relaxant), and naltrexone (hydrochloride salt) [6, 7]. Intrathecal injections of delayed-release steroids such as triamcinolone acetonide (TCA) are a therapeutic option for MS patients with predominantly spinal cord symptoms such as spasticity [8]

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