The Use of High Initial Doses of Botulinum Toxin Therapy for Cervical Dystonia Is a Risk Factor for Neutralizing Antibody Formation-A Monocentric Cross-Sectional Pilot Study.

Harald Hefter,Max Schomaecker,Sara Samadzadeh,Dietmar Rosenthal,Isabelle Schomaecker

doi:10.3390/medicina58010088

Abstract

Background and Objectives: The present study aims to analyze the complex patient/treating physician interaction at onset of botulinum toxin (BoNT) therapy in patients with idiopathic cervical dystonia (CD) and the influence of high initial doses on long-term outcomes. Materials and Methods: A total of 74 CD patients with well-documented courses of BoNT treatment were consecutively recruited after written informed consent. Patients had to rate the amount of improvement of CD in percent of severity of CD at onset of BoNT therapy. They had to draw the course of disease severity (CoD) of CD from the onset of symptoms until the onset of BoNT therapy and from the onset of BoNT therapy until recruitment. The remaining severity of CD was estimated by the treating physician using the TSUI score. Demographic- and treatment-related data were extracted from the charts of the patients. Seventeen patients with suspected secondary treatment failure (STF) were tested for the presence of antibodies. Results: Depending on the CoD before BoNT therapy, three patient subgroups could be distinguished: rapid onset, continuous onset and delayed onset groups. Time to BoNT therapy, increase in dose and improvement were significantly different between these three groups. In the rapid onset group, with the highest initial doses, the best improvement was reported, but the highest number of patients with an STF and with neutralizing antibodies was also observed. Conclusion: The use of high initial doses in the BoNT therapy of CD is associated with a rapid response and quick success; however, it leads to an elevated risk for the development of a secondary treatment failure and induction of neutralizing antibodies.

Highlights

Cervical dystonia (CD) is the most frequent type of focal dystonia [1,2,3]
A therapy of choice is a course of intramuscular injections of botulinum neurotoxins (BoNTs), which have to be performed on a regular basis every 3–4 months to achieve a stable plateau of improvement [10,11]
The immune system of the patients is repeatedly confronted with the traumatic application of a bacterial product, which may lead to the detection of epitopes of the 150 kDa large neurotoxin by dendritic cells, B-cell stimulation and the risk of formation of neutralizing antibodies (NABs) [12]

Summary

Introduction

Cervical dystonia (CD) is the most frequent type of focal dystonia [1,2,3]. CD manifests around midlife, affects about twice as many females compared with males [1] and results from muscular hyperactivity in the shoulder and neck muscles [1,3,4]. Patients may claim a broad spectrum of symptoms, such as pain, muscular hypertension, abnormal position of head and shoulders and tremors and myoclonic jerks [5,6]. These symptoms interfere with everyday life activities and have an impact on social interactions and emotional wellbeing [2,7,8,9]. Patients had to rate the amount of improvement of CD in percent of severity of CD at onset of BoNT therapy. They had to draw the course of disease severity therapy until recruitment. Time to BoNT therapy, increase in dose and improvement were significantly different between these three groups

Methods

Results

Discussion

Conclusion