From clues to mechanisms

Abstract

Amyotrophic lateral sclerosis (ALS) is the most common degenerative disease of motor neurons. Its causes are not known. Genetic and environmental risk factors have been identified.1,2 Over 90% of patients are considered sporadic because they have no similarly affected relatives. ALS usually starts in one part of the body. It spreads horizontally by contiguity—shown recently to occur independently at the spinal and cortical levels3—and vertically up and down the motor neuron system to involve first-, second-, and third-order motor neurons.2 Most patients enter a linear phase in which rate of loss of muscle strength is fairly constant.4 In this issue of Neurology ®, Sabatelli et al.5 report a distinctive phenotype among their patients with onset age 40 years or younger (“young adults”): men with predominantly upper motor neuron (UMN) involvement and longer survival. Among 57 young adult patients, 59.6% had a predominantly UMN phenotype. The ratio of men to women among those with this phenotype was …