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Techniques to estimate motor unit number (MUNE) measure the number of functioning motor units in a muscle. As amyotrophic lateral sclerosis (ALS) is characterized by progressive motor unit loss, this disease offers an ideal setting for the use of MUNE. Statistical MUNE was employed in a recent multicenter trial of creatine in ALS, and was shown to be reliable, reproducible, and to decline with disease progression. However, motor unit amplitude stayed constant over 7 months, a finding believed to reflect an artifact of the method. The statistical method was revised to reflect more accurately the presence of larger motor units and employed in a 12-month study of Celecoxib in ALS. MUNE declined by 49% in 12 months; however, motor unit amplitude again stayed constant over the same period. Statistical MUNE estimates motor unit number based on the variability of response to a repeated stimulus of constant strength, with an underlying assumption that this variability is due solely to the number of motor units responding in an intermittent manner. Based on studies showing that single motor units in ALS display excessive amplitude variability when stimulated repeatedly, we show that response variability in ALS patients is in large part due to single unit changes. Thus, we conclude that the statistical method is not an appropriate measure of motor unit number in any disease associated with motor unit instability. Muscle Nerve, 2006

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