Botulinum Neurotoxin (BoNT) trial

Botulinum neurotoxin (BoNT) has emerged as a useful therapy for several hyperkinetic movement disorders, especially dystonia. Previous research and our own clinical experience suggest that treatment with BoNT is an effective therapy for jerky movements as well. In this project, we will study the effect of BoNT on functional jerky movement disorders.

Functional movement disorders cannot be accounted for by a known neurologic syndrome. At least 2–9% of patients seen in movement disorder clinics suffer from psychogenic movement disorders and a substantial part has jerks. Therapy currently focuses on frequently co-occurring psychiatric disease, but results are poor. Because evidence that the distinction between organic and functional disease is not clear cut is increasing, other treatment options are considered for functional movement disorders.

Hypothesis

Administration of BoNT is an effective treatment for functional jerks that significantly compromise patients.

Study objectives

We will study the effect of BoNT on functional jerks by assessing 1. improvement in jerk severity assessed with the Clinical Global Impression - Improvement scale (primary outcome measure); 2. Motor symptom severity and disease burden; 3. disability and daily functioning and 4. co-existent psychiatric symptoms. Also the effects of treatment on brain activity were assessed in a small group of patients using fMRI. Further, neurophysiological measurements of fear and arousal were measured using the auditory startle reflex.

Materials and methods

A phase II single-center double blind randomized placebo-controlled trial will be performed. We will include 24 patients with at least one disabling functional jerk in each treatment arm. Patients will be injected with BoNT up to two times during the trial. Assessments will include standardized scales based on video-tapes. The effect of BoNT after 1 year of treatment will be evaluated subsequently in an open-label study.

Expected results

Inclusion is finished an results will be expected in 2018. This study will provide evidence on a promising new therapeutic option for functional jerks, a prevalent movement disorders for which results of current therapies are poor. Registration can be found in the Netherlands Trial Registry (NTR 2478).

Trial protocol

Team

Y.E.M. Dreissen, PhD-student (y.e.dreissen@amc.uva.nl)

J.M. Gelauff, PhD-student

Dr. J.M. Dijk, epidemiologist

Dr. JHTM Koelman, investigator

Prof. MAJ Tijssen, principal investigator