Amyotrophic lateral sclerosis (ALS): new insights 156 years after Charcot's masterful description.

Abstract: In 1869, Charcot and Alix Joffroy published the first detailed clinical and neuropathological description of amyotrophic lateral sclerosis (ALS), establishing the correlation involving muscle weakness, atrophy, spasticity, and degeneration of the lateral corticospinal tracts. Charcot unified the involvement of upper and lower motor neurons into a single clinical entity. His pioneering description was limited to the motor system, reflecting the scientific constraints of his time. Charcot interpreted ALS primarily as a disorder of the motor system, a conclusion consistent with the clinical and pathological methods available in the late nineteenth century. Neurological investigation at that time relied mainly on detailed clinical observation, anatomical correlation at autopsy, and relatively-simple physiological techniques. These approaches were well suited to identify motor dysfunction but were far less capable of revealing subtle cognitive or behavioral alterations. Currently, ALS is recognized as a multisystem neurodegenerative disorder. Thus, Charcot's historical contribution was crucial for the initial understanding of ALS, while modern perspectives acknowledge its broader clinical complexity beyond the motor system.