Application of clinical neurophysiology to clinical trials involving motor neuron diseases

Abstract

Publisher Summary This chapter discusses the clinical neurophysiological assessment of lower motor neuron loss in amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA). Motor neuron diseases (MNDs) are defined by different patterns of upper and lower motor neuron loss. The major forms of MNDs include ALS, which involves degeneration of upper and lower motor neurons; SMA, which involves degeneration of lower motor neurons; and primary lateral sclerosis (PLS), which involves degeneration of upper motor neurons. The chapter discusses the pathophysiology consequent to neuronal loss and the advantages and limitations of clinical neurophysiological tests that have been used. The application of clinical neurophysiology to clinical trials for MND include determining natural rates of progression, making predictions about rates of progression, and serving as endpoint measures. The collective clinical trial experience with summed maximal voluntary isometric contraction (MVIC) and functional scales in clinical trials is greater than for clinical neurophysiological tests, and the utility of neurophysiological testing has not been fully explored. The challenges of clinical neurophysiological tests as endpoint measures in clinical trials are discussed.