Amyotrophic lateral sclerosis: lower motor neuron disease spreading to upper motor neurons

Contrary to the recently reemphasized notion that the primary neuron involved in amyotrophic lateral sclerosis (ALS) is the cortical (upper) motor neuron (UMN), we believe that the lower motor neuron (LMN) is primarily involved by the retrograde transport of pathogens from neuromuscular junctions, and the disease process spreads monosynaptically to the UMN. Pathologically and epidemiologically, the LMN hypothesis is more logical than the UMN in light of the recent understanding of neuroaxonal transport systems, particularly in regard to anterograde cytoskeleton transport and the kinetics of the force promoting slow axonal transport. By correlating the early pathologic findings, i.e., the swelling of the initial axons and formation of intracytoplasmic inclusions in the LMN, ALS may be regarded as a disease of axonal transport, especially its slow component (SCa). Therapeutic intervention to facilitate SCa should be attempted in ALS.