Tracking motor neuron loss in a set of six muscles in amyotrophic lateral sclerosis using the Motor Unit Number Index (MUNIX): a 15-month longitudinal multicentre trial.
BACKGROUND
Motor Unit Number Index (MUNIX) is a novel neurophysiological measure that provides an index of the number of functional lower motor neurons in a given muscle. So far its performance across centres in patients with amyotrophic lateral sclerosis (ALS) has not been investigated.


OBJECTIVE
To perform longitudinal MUNIX recordings in a set of muscles in a multicentre setting in order to evaluate its value as a marker of disease progression.


METHODS
Three centres applied MUNIX in 51 ALS patients over 15 months. Six different muscles (abductor pollicis brevis, abductor digiti minimi, biceps brachii, tibialis anterior, extensor dig. brevis, abductor hallucis) were measured every 3 months on the less affected side. The decline between MUNIX and ALSFRS-R was compared.


RESULTS
31 participants reached month 12. For all participants, ALSFRS-R declined at a rate of 2.3%/month. Using the total score of all muscles, MUNIX declined significantly faster by 3.2%/month (p ≤ 0.02). MUNIX in individual muscles declined between 2.4% and 4.2%, which differed from ASLFRS-R decline starting from month 3 (p ≤ 0.05 to 0.002). Subgroups with bulbar, lower and upper limb onset showed different decline rates of ALSFRS-R between 1.9% and 2.8%/month, while MUNIX total scores showed similar decline rates over all subgroups. Mean intraclass correlation coefficient for MUNIX intra-rater reliability was 0.89 and for inter-rater reliability 0.80.


CONCLUSIONS
MUNIX is a reliable electrophysiological biomarker to track lower motor neuron loss in ALS.
Neuromuscular Diseases Unit/ALS Clinic, Kantonsspital St.Gallen, St.Gallen, Switzerland.
Christoph
C
Neuwirth
Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Paul E
PE
Barkhaus
Neuromuscular Diseases Unit/ALS Clinic, Kantonsspital St.Gallen, St.Gallen, Switzerland.
Christian
C
Burkhardt
Department of Neurosciences, Faculty of Medicine, Hospital de Santa Maria, Instituto de Medicina Molecular, University of Lisbon, Lisbon, Portugal.
José
J
Castro
Kantonsspital Winterthur, Winterthur, Switzerland.
David
D
Czell
Department of Neurosciences, Faculty of Medicine, Hospital de Santa Maria, Instituto de Medicina Molecular, University of Lisbon, Lisbon, Portugal.
Mamede
M
de Carvalho
Natus Medical Incorporated, Middleton, Wisconsin, USA.
Sanjeev
S
Nandedkar
Department of Clinical Neurophysiology, Institute of Neurosciences, Uppsala University, University Hospital, Uppsala, Sweden.
Erik
E
Stålberg
Neuromuscular Diseases Unit/ALS Clinic, Kantonsspital St.Gallen, St.Gallen, Switzerland Department of Neurology, University Hospital Basel, Basel, Switzerland.
Markus
M
Weber
D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000473:pathology*; D015331:Cohort Studies; D018450:Disease Progression; D004576:Electromyography; D005260:Female; D007839:Functional Laterality; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009046:Motor Neurons / Q000473:pathology*; D018482:Muscle, Skeletal / Q000473:pathology*; D015588:Observer Variation; D015203:Reproducibility of Results; D016896:Treatment Outcome