Fine structural observations of neurofilamentous changes in amyotrophic lateral sclerosis

Twenty-two of 32 sporadic cases of amyotrophic lateral sclerosis had argyrophilic spheroids, 20 micrometers or larger, in the anterior horns of the spinal cords. The fine structure of these spherical bodies was characterized by interwoven, small bundles of 10 nm neurofilaments. Scattered mitochondria, vesicles and fragments of smooth endoplasmic reticulum were commonly found among the bundles of neurofilaments. The spheroids were present not only in the myelinated axons, but also in the perikarya of the anterior horn cells. In anterior horn neurons occasional fragments of rough endoplasmic reticulum, lipofuscin and even nuclei were found among the neurofilaments, in addition to the other components. Rarely, some filamentous accumulations contained unusual features such as paracrystalline arrays, polyglucosan bodies and honeycomb-like structures. Linear densities, associated with ribosome-like particles, were found scattered within focal collections of randomly arranged neurofilaments in some perikarya of two cases. Occasional mitochondria with regularly arranged short protrusions on the outer membrane were observed in the myelinated axons in one case.