Objective Measurements of Upper and Lower Motor Neuron Loss in Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive disease with an average surviving time of 3 to 5 years. The hallmarks of the pathological changes are loss of lower motor neurons in the spinal cord and upper motor neurons(UMN) in the motor cortex. However, structural MRI studies of the spinal cord and the brain often fail to show any changes. Due to lack of objective and quantitative markers for upper and lower motor neuron losses, all clinical trials use clinical measures to monitor the disease progression and therapeutic effects. However, these clinical measures may not reliably assess the upper and lower motor neuron losses. For example, two clinical trials of Riluzole in ALS used survival time and changes in functional status as the primary efficacy outcomes. In other clinical trials, the Tuft Quantitative Neurological Examination was used to measure effectiveness. There is no surrogate marker for diagnosing ALS, monitoring disease progression or checking therapeutic effects. Therefore, physiological and objective methods would be extremely valuable in evaluating the function of lower motor neurons and upper motor neurons in ALS, identifying disease process and monitoring the effects of potential therapeutic agents. Motor unit number estimate (MUNE) physiologically assesses lower motor neuron loss