Pathology of motor neurons in accelerated hereditary canine spinal muscular atrophy.

Hereditary canine spinal muscular atrophy is a dominantly inherited lower motor neuron disease with three phenotypic variants: accelerated, intermediate, and chronic. Pups with the accelerated disease develop weakness by 1.5 months and are quadriparetic by 3 months. The motor neurons of selected brainstem nuclei and ventral horn of the spinal cord are characterized by chromatolysis and by neurofibrillary abnormalities in perikarya, dendrites, and, most strikingly, proximal axons. Dendrites and axons are segmentally enlarged by accumulations of maloriented fascicles of neurofilaments; the axonal swelling usually involve internodes and are delimited by the initial segment or nodes of Ranvier. The disorganized neurofilaments appear to entrap mitochondria and other particular organelles. We have hypothesized that the neurofibrillary changes in this genetic disorder in dogs is associated with an abnormality of the cytoskeletal constituents of motor neurons. Hereditary canine spinal muscular atrophy shows features in common with human motor neuron disease.