Motor unit number estimation (MUNE) in diseases of the motor neuron: utility and comparative analysis in a multimodal biomarker study.
We prospectively studied 64 patients with motor neuron disease (amyotrophic lateral sclerosis (ALS), familial ALS (fALS), progressive muscular atrophy (PMA) and primary lateral sclerosis (PLS)) using multiple point stimulation motor unit number estimation (MUNE), transcranial magnetic stimulation (TMS), proton magnetic resonance spectroscopic imaging (1H MRSI), diffusion tensor imaging (MRDTI), and clinical measures at baseline and every 3 months thereafter for 15 months. Substantial differences in MUNE were noted among the motor neuron disease subgroups (P = 0.0005) and mean values for each motor neuron disease subgroup were significantly lower vs. controls (ALS = 76, fALS = 80, PMA = 29, and PLS = 174) vs. the normal control average (267). MUNE correlated well with % FVC (r = 0.32; P = 0.01), manual muscle testing (r = 0.52; P < 0.0005), grip strength (r = 0.34; P = 0.007), and pinch strength (r = 0.49; P < 0.0005). Overall, MUNE showed the greatest significant change over time of any measure, clinical or otherwise, tested in this study (-2.35 linear trend % change per month, mean). MUNE clearly delineates lower motor neuron dysfunction, strongly correlates with important clinical functions (such as strength and respiration) and is a highly sensitive marker of disease progression over time. These features make MUNE an important tool for both the study of the pathophysiology of the motor neuron diseases, as well as an important measure for incorporation into future clinical trials.
Gooch
Clifton L
CL
Department of Neurology, University of South Florida College of Medicine, Tampa, FL 33612, USA. cgooch@health.usf.edu
Pullman
Seth L
SL
Shungu
Dikoma C
DC
Uluğ
Aziz M
AM
Chane
Stephen
S
Gordon
Paul H
PH
Tang
Ming X
MX
Mao
Xiangling
X
Rowland
Lewis P
LP
Mitsumoto
Hiroshi
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D015415:Biomarkers / Q000378:metabolism*; D004576:Electromyography; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D008875:Middle Aged; D016472:Motor Neuron Disease / Q000473:pathology* / Q000503:physiopathology; D009046:Motor Neurons / Q000502:physiology*; D011522:Protons; D013223:Statistics as Topic; D050781:Transcranial Magnetic Stimulation / Q000379:methods
D015415:Biomarkers; D011522:Protons