High-Density Surface EMG Guided Botulinum Toxin Injection - Effect on the Compound Muscle Action Potential Recorded from the Extensor Digitorum Brevis Muscle

The effect of Botulinum Toxin (BTX) is based on the neuromuscular blockade of
cholinergic fibers of the peripheral nervous system. Since the introduction of
BTX type A (BTXA) into therapeutic medicine, the use of this drug has been
widely expanded to many medical disciplines and indications. Clinical
observations and experimental studies revealed an effect of BTX not only on the
target muscle, but also on adjacent (untreated) muscles. Experimental studies
have proven that local peripheral diffusion of BTX is a major causative factor
for this side-effect. Peripheral diffusion is mainly a problem in areas in
which multiple muscles have a close topographical relationship, as e.g. in the
face and neck. Limiting the dose of BTX in such critical anatomical areas has
turned out to be helpful in reducing untoward spread of toxin to other muscles
(called *toxin jump*). A plausible strategy to reduce the side-effect problem
without diminishing the efficacy of BTX in the target muscle is to inject a
lower dose of the toxin only in the area of its action (i.e. in the endplate
region). High-density surface electromyography (HDsEMG) allows a precise and
reliable endplate zone localization. Using this electrophysiological technique,
endplate zone locations and distributions could be successfully specified in
several muscle groups. Using a recently developed HDsEMG electrode grid, BTX
injection is even possible through holes in between the sensor so that marking
of the endplate zone and removal of the grid prior to injection is not
necessary.

The aim of this pilot study is to evaluate whether precise HDsEMG-guidance
improves the therapeutic effect of BTXA. Because of its minor functional
importance and focused endplate distribution, the extensor digitorum brevis
(EDB) muscle is selected for this investigation. Moreover, this muscle has
already shown in previous studies to be suitable for such a model. To achieve
only a local toxin administration, only a minimal effective dose of the toxin
will be administered (from a higher dose we would not expect a positive effect
of precise administration near the endplates due to diffusion of the drug
throughout the main part of the muscle). As a gradual measure of the
therapeutic effect of the toxin, we compare changes in the amplitude of the
compound muscle action potential (CMAP) in response to supra-maximal
stimulation of the peroneal nerve.
We hypothesize, that with a precise injection in the endplate region, a better
therapeutic effect can be achieved than on the control site in which an
injection of the same dose into the (anatomically defined) center of the EDB
muscle is performed.

1. In a preliminary experiment (4 subjects) we will verify if a dose of 30 IU
actually leads to a +/- 50% CMAP amplitude reduction measured at day 30 after
HDsEMG guided BTXA injection in endplate region of the EDB muscle (as can be
expected from previous studies).
2. Control study of the therapeuthic effect of BTXA injection with HD-sEMG
guidance (study side) and without HD-sEMG guidance (contralateral muscle of the
same subject). Subjects are followed longitudinally on 4 occasions (baseline,
week 2, 8, and 12) to consider the time-dependent effect of BTXA.

On the study side the injection of BTXA takes place under guides of HDsEMG. On
the control side this is done without the knowledge of where the endplate
position is.

The EDB muscle is of little use in daily life. A reduction in the force of this
muscle has no functional impact for the participant. BTXA injection in the EDB
muscle has no known risks involved. The measurement of the CMAP involves
electrical stimulation of the nerve. This is a standard clinical technique that
causes negligible discomfort.