Motor unit number estimation predicts disease onset and survival in a transgenic mouse model of amyotrophic lateral sclerosis.
Motor unit number estimation (MUNE) has proved useful in predicting rate of progression and survival in patients with amyotrophic lateral sclerosis (ALS). In animal models, it has demonstrated physiological effects of experimental medications that were not evident behaviorally. We sought to determine more specifically what aspects of function and survival that MUNE could predict in the G93A transgenic mouse model of ALS. Transgenic mice were examined in two distinct treatment studies, neither of which showed an effect of drug on survival, behavioral measures, or MUNE. MUNE was performed using a modification of the incremental stimulation method by stimulating the sciatic nerve at the sciatic notch, and recording with a circumferential surface electrode around the ipsilateral distal hindlimb. Both limbs were studied and the results averaged. MUNE was performed longitudinally on all animals from near onset to premorbid state. Each study was evaluated separately. For both studies, MUNE at initial study correlated significantly with behavioral determination of disease onset, and MUNE slope from initial to final study correlated significantly with disease duration, as measured from onset to time of death. However, the final MUNE value did not correlate with survival. Thus, in two studies involving animals with quite different disease courses, initial MUNE effectively predicted symptom onset and MUNE slope predicted survival. This suggests that MUNE has potential efficacy as a useful functional outcome measure in both animal and human studies of ALS.
Shefner
Jeremy M
JM
Department of Neurology, Upstate Medical University, Syracuse, New York 13210, USA. shefnerj@upstate.edu
Cudkowicz
Merit
M
Brown
Robert H
RH
D017668:Age of Onset; D000690:Amyotrophic Lateral Sclerosis / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology*; D000818:Animals; D002452:Cell Count / Q000379:methods; D004195:Disease Models, Animal; D018450:Disease Progression; D042241:Early Diagnosis; D004558:Electric Stimulation / Q000379:methods; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000473:pathology / Q000502:physiology*; D018485:Muscle Fibers, Skeletal / Q000473:pathology / Q000502:physiology*; D018482:Muscle, Skeletal / Q000294:innervation / Q000473:pathology / Q000503:physiopathology*; D009469:Neuromuscular Junction / Q000503:physiopathology*; D011237:Predictive Value of Tests; D011379:Prognosis; D013482:Superoxide Dismutase / Q000235:genetics; D015996:Survival Rate / Q000639:trends
C109415:SOD1 G93A protein; D013482:Superoxide Dismutase