We described 2 cases and presented new experimental data on the study of the etiopathogenesis of amyotrophic leukospongiosis (AL) using Western blot, electronic and atomic force microscopy. AL is characterized by the gradual and steady progression of flaccid paralysis of extremities and muscles of the trunk without the expressed atrophy with an inevitable fatal outcome resulting in breathing disorders of spinal type, degenerative changes of the central nervous system and, first of all, spongiosis of the white matter of the brain. Several lines of evidence suggest that the accumulation of pathological prion protein (PrPAL) in the human brain is a critical event for the development of the disease. The new findings add knowledge of the AL etiopathogenesis and support the evidence that the disease is caused by prion infection and refers to the group of transmissible spongiform encephalopathies.