Ocular vestibular evoked myogenic potentials in patients with myasthenia gravis

Myasthenia Gravis (MG) is a disease characterized by fatigable muscle weakness
caused by impairments in neuromuscular transmission. Recent studies show that
impaired neuromuscular transmission may be detectable in ocular muscles by
measuring ocular vestibular evoked myogenic potentials (oVEMPs). These
potentials are evoked by applying a short (4 ms) vibration to the forehead. The
amplitude of the oVEMP declines after repetitive stimulation in patients with
impaired neuromuscular transmission (also known as a decrement), whereas it
remains stable in healthy subjects. The application of the oVEMP in the
diagnosis of MG is relatively new, but case-control studies show that this is
an useful test, which is non-invasive and virtually without any burden for the
patient.1, 2 This test holds great promise for two reasons. Firstly, it is the
first test to measure neuromuscular transmission of the extra-ocular muscles,
which are the most frequently affected muscles in MG, that are often involved
early in the course of the disease. In about 10% of the MG patients the disease
remains restricted to isolated weakness of the extra-ocular muscles. Secondly,
unlike currently used tests, it does not require electrical nerve stimulation
and is non-invasive as only a vibration is used to elicit the oVEMP.

1. The primary objective of this study is to confirm the utility of the oVEMP
cross-sectionally for the diagnosis of MG by reproducing the findings of Valko
et al. in our cohort of MG patients and three control groups: healthy controls,
controls with other neuromuscular diseases and controls with non-neuromuscular
diseases that can cause diplopia. (Cross-sectional study)
2. Secondly, we want to investigate the diagnostic value of the oVEMP
longitudinally in patients with myasthenia gravis in the differential
diagnosis. (Longitudinal study)
3. Thirdly, we want to study whether the oVEMP decrement responds to treatment
with acetylcholinesterase inhibitors. (Neostigmine study)
4. Finally, we want to study the reproducibility of the oVEMP decrement in
healthy controls and patients.

A cross-sectional study will be performed on patients with MG and three control
groups: healthy controls, controls with other neuromuscular diseases and
controls with non-neuromuscular diseases that can cause diplopia. The aim of
this cross-sectional study is to conform the utility of the oVEMP test for
diagnostic use and to establish a threshold value for diagnostic use (using a
ROC curve). Simultaneously a longitudinal study will be performed in patients
with the clinical suspicion of MG. All patients are tested with the oVEMP test.
By correlating the outcome of the oVEMP test with the final diagnosis, the
clinical utility of the oVEMP test can be verified using the threshold value
calculated by the cross-sectional study. Furthermore, we will perform the oVEMP
test in patients before and after the administration of acetylcholinesterase
inhibitors, which is already administered for diagnostic purposes in routine
clinical care. Lastly, we want to study the reducibility of the outcome measure
decrement, by performing the measurement twice in a subgroup of patients.

The risks associated with participation can be considered negligible and the
burden can be considered minimal, because the study only involves asking the
patients to look in two directions for 60 seconds and a measurement with a
minimal intervention (applying non-harmful vibration to the head with a
hand-held mini-shaker and a small number of skin electrodes). The intensity of
the vibration is comparable with the vibration of an electrical toothbrush. In
the future patients may benefit from these investigations because the newly
developed tool is expected to aid in the diagnosis of MG.