Clinical Spectrum of Amyotrophic Lateral Sclerosis (ALS)
- 1Djavad Mowafaghian Centre for Brain Health, Department of Medicine (Neurology), University of British Columbia, Vancouver V6T 2B5, Canada
- 2Montreal Neurological Institute and Hospital, McGill University, Montréal H3A 2B4, Canada
- 3Department of Neurosciences, University of California, San Diego, La Jolla, California 92093
- Correspondence: jravits{at}ucsd.edu; neil.cashman{at}vch.ca
Abstract
Amyotrophic lateral sclerosis (ALS) is primarily characterized by progressive loss of motor neurons, although there is marked phenotypic heterogeneity between cases. Typical, or “classical,” ALS is associated with simultaneous upper motor neuron (UMN) and lower motor neuron (LMN) involvement at disease onset, whereas atypical forms, such as primary lateral sclerosis and progressive muscular atrophy, have early and predominant involvement in the UMN and LMN, respectively. The varying phenotypes can be so distinctive that they would seem to have differing biology. Because the same phenotypes can have multiple causes, including different gene mutations, there may be multiple molecular mechanisms causing ALS, implying that the disease is a syndrome. Conversely, multiple phenotypes can be caused by a single gene mutation; thus, a single molecular mechanism could be compatible with clinical heterogeneity. The pathogenic mechanism(s) in ALS remain unknown, but active propagation of the pathology neuroanatomically is likely a primary component.
