A novel neurophysiological measurement (MUNIX) in neuromuscular disorders; test-retest reliability and longitudinal follow up measurements in ALS patients

An objective measure of disease progression and therapeutic response is sorely
needed for neuromuscular disorders like Amyotrophic Lateral Sclerosis (ALS).
The ideal marker should be sensitive, reliable, non- invasive as well as
cost-effective and with respect to ALS drug trials, correlate with clinical
findings and reflect disease progression.For instance quantitative
neuromuscular examinations, measurement of pulmonary function, disability
scales, and survival, are limited by variability due to several poorly
controlled factors. By contrast neurophysiological methods such as the compound
muscle action potential (CMAP) amplitudes and motor unit estimates (MUNEs) have
the great advantage of being less dependent on the patient*s motivation,
cooperation and fatigue. They are probably the most objective quantitative
tests currently available and therefore provide potential markers of disease
progression. MUNE techniques have the advantage that they can show motoneuron
loss already in the early stages of ALS, while CMAP amplitude do not change
until 50% of motor units are lost (Bromberg 2008). However, MUNE techniques
also have disadvantages. Most of the techniques are time-consuming allowing
only few muscles to be studied in a clinical setting.
The major advantages of the novel MUNIX technique are that it is non-invasive,
quickly to perform, technically not very challenging and that it can be applied
to any proximal or distal muscle, in which a CMAP after supramaximal electrical
stimulation can be evoked (Nandedkar 2004).
First results that are reported are promising but a study on inter-rater and
intra-rater variability and relation with clinical variables in ALS patients is
lacking.

Primary
To investigate the inter-rater and intra-rater variability of a novel
neurophysiological measurement (Motor Unit Number Index, MUNIX) for estimation
of functioning motor units, in healthy controls and ALS patients
Secondary
To evaluate the feasibility and reliability of MUNIX measurements as a
potential surrogate marker for ALS clinical trials.

This is an observational study that determines the outcome of questionnaire and
electrofysiological measures.

Several demographic data are gathered (see protocol). MUNIX is measured on 5
different muscles. For MUNIX measurements some degree of cooperation of
subjects is inevitable. The same experienced investigator will perform all
MUNIX studies in subjects twice with a break of minimum 30 minutes between each
session (intra-rater-reliability). ALS patients will be followed over a periode
of maximally 12 months with an interval of 3 months. MUNIX measurements are
non-invasive. The electrical stimulus needed to measure the CMAP and MUNIX is a
standard technique in clinical neurophysiology used on a daily basis that has
no known negative consequences. Patients may feel slightly fatigued because of
the short maximal contractions. Echointensity is measured at baseline and after
6 and 12 months as structural changes in the muscle occur at a slower rate.