Abstract

Lewy body-like hyaline inclusions (LBI), Bunina bodies (BB) and central chromatolysis are characteristic neuropathological features of spinal motor neurons in amyotrophic lateral sclerosis (ALS). Using histometric methods, we studied the spinal motor neurons of 4 patients with sporadic ALS and 3 neurological control patients to determine the possible relationship between these neuropathological features and cytoplasmic, nuclear and nucleolar size. In an ALS patient with a very rapid clinical course, many neurons with LBI were observed. Enlargement of nucleolar size and the nucleolar/nuclear ratio of neurons with LBI or BB were the only histometric difference compared to those of normal-appearing neurons. In ALS patients with an average clinical course, the number of neurons with LBI was lower, the number of neurons with BB was higher, and the nuclear and nucleolar sizes were smaller than those of normal-appearing neurons, particularly in chromatolytic neurons without LBI or BB. These data raise the possibility that motor neurons with LBI may represent an early stage in the neurodegenerative process, when the rate of protein synthesis is elevated as evidenced by their larger nucleolar size. Thus, the causative agent(s) of ALS may initially stimulate protein synthesis while in turn leading to down regulation of certain luxury function genes, culminating in neuronal dysfunction and death.