It was l suggested a long time ago, that ALS is rather a cortical than a spinal disease. The work of Heiko Braak and collaborators has demonstrated neuropathological evidence that a cortical origin of the disease is a very likely one. This paper discusses this evidence from a translational perspective. It includes a discussion of the clinical syndrome of ALS, including frontal deficits and oculomotor involvement. Also, neuroimaging evidence is discussed from a translational perspective.
ALS, Motorcortex, Initiation and Propagation of ALS, extramotor involvement in ALS
Braak H, Brettschneider J, Ludolph AC, et al. Amyotrophic lateral sclerosis--a model of corticofugal axonal spread. Nat Rev Neurol. 2013 Dec;9(12):708-14.
Brettschneider J, Del Tredici K, et al. Stages of pTDP-43 pathology in amyotrophic lateral sclerosis. Ann Neurol. 2013 Jul;74(1):20-38.
Kassubek J, Müller HP, Del Tredici K, et al. Diffusion tensor imaging analysis of sequential spreading of disease in amyotrophic lateral sclerosis confirms patterns of TDP-43 pathology. Brain. 2014 Jun;137(Pt 6):1733-40