Primary lateral sclerosis

Like motor neuron diseases (MNDs) refer to a constellation of primarily sporadic neurodegenerative diseases characterized by a progressive loss of upper and/or lower motor neurons. Primary lateral sclerosis (PLS) is considered a neurodegenerative disorder that is characterized by a gradually progressive course affecting the central motor systems, designated by the phrase "upper motor neurons." Despite significant development in neuroimaging, neurophysiology, and molecular biology, there is a growing consensus that PLS is of unknown etiology. Currently there is no disease-modifying treatment for PLS, or prospective randomized trials being carried out, partly due to the rarity of the disease and lack of significant understanding of the underlying pathophysiology. Consequently, the approach to treatment remains largely symptomatic. In this chapter we provide an overview of primary lateral sclerosis including clinical and electrodiagnostic considerations, differential diagnosis, updates in genetics and pathophysiology, and future directions for research.