cord and brainstem spinocerebellar pathways. Neuronal loss may even occur within Clarke's column, the thalamus, the corpus callosum, and the superior colliculi. Magnetic resonance imaging studies have demonstrated high intensity lesions widely distributed within the central nervous system white matter. In addition, sural nerve biopsies have shown evidence of axonal atrophy and remyelination involving, in particular, the larger diameter nerve fibers (Swash & Schwartz, 1992, pp. 4-13).
Histological analyses have found numerous intraneuronal inclusions associated with ALS. Bunina (cited in Swash & Schwartz, 1992, p. 11) described intracytoplasmic acidophilic inclusions, 2-3 (m in diameter. These amorphous, vesicular Bunina bodies are often found in the perikarya, axon, and soma of ALS patients' motor neurons. In addition, spheroids composed of individually arranged or bundled neurofilamentous material have also been observed. Finally, the heat shock protein, ubiquitin, may associate with intermediate filament inclusion bodies to form either aggregates or skein-like cytoplasmic arrays. Unfortunately, though, the pathogenesis and significance of these intraneuronal inclusions remain unknown.
Nonspecific pathological changes associated with ALS generally result from the degeneration of patients' central neurons. For example, ALS patients' skeletal muscle may exhibit signs of denervation and reinnervation. Patten et al. (cited in Swash & Schwartz, 1992, p. 5) found that the
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