Natural history of ALS: symptoms, strength, pulmonary function, and disability.

Abstract

ALS is a disease that may have a preclinical and a clinical phase (see Appendix 1 Table 1). The low frequency of ALS suggests an inherent susceptibility in patients who are destined to develop the disease at a particular point in life subsequent to a possible initiating event. [1] View this table: Table 1. Appendix 1: Pathogenetic aspects of ALS. Neuropathological, neurophysiological, and clinical aspects of ALS in the preclinical and clinical stages. There is currently no clear-cut evidence of neuropathologic, neurophysiologic, or clinical abnormalities that would mark a patient as potentially susceptible to ALS during the susceptibility period. Initiating events may include severe electric shock exposure, which is a physical injury that is epidemiologically linked to the development of ALS, or dietary intake of particular substances that have, in isolated instances, been associated by case-control studies with the development of ALS. During the latent period of the development of the disease, there may be changes in motoneuron soma and dendritic size as the only neuropathologic features long before there is evidence of motoneuron loss or corticospinal tract degeneration. No clear-cut neurophysiologic signs have yet been described. [2] During the clinical period of the disease, there may be a presymptomatic period during which there are pathologic changes involving motoneuron size and loss as well as possible corticospinal tract degeneration. This hypothetical construct is based on pathologic studies. [3] Neurophysiologic changes during this time may include changes in single-fiber density, with variable changes in motor unit count. [4] The clinical examination at this point is characterized by patient reports of possible functional changes and by possible abnormalities in isokinetic muscle testing at a time when normal isometric strength is present. [5] During the stage of disease spread from focal onset to more symmetric generalization, there will be changes in motoneuron size and loss as …