[Neuropathology of amyotrophic lateral sclerosis--from basic findings to topics]

Amyotrophic lateral sclerosis (ALS) is a relentlessly progressive neurodegenerative disease that selectively affects upper and low motor neurons (UMNs and LMNs). The remaining LMNs show, in addition to normal appearance, a variety of cell pathology such as central chromatolysis, atrophy of the cell body and processes, Bunina bodies, and ubiquitinated hyaline and skein-like inclusions. Ultrastructural studies of the last two profiles indicate their processing by lysosomes. Whether apoptosis is responsible for motoneuronal death in ALS or not remains to be determined. In Klüver-Barrera (KB) staining, the pyramidal tracts in ALS usually appear normal at the pons in spite of their obvious pallor at the lower levels, leading to the dying-back hypothesis. However, axonal staining in such cases reveals obvious loss of large axons in the pontine pyramidal tracts, a finding inconsistent with the hypothesis. Similarly, in cases of motoneuron disease with the pyramidal tracts well stained by KB method, therefore, 'spinal progressive muscular atrophy (SPMA)', axonal staining demonstrated patent loss of large axons there. Thus, reappraisal seems to be required for previously reported SPMA cases, whose pathological diagnosis used to be made by KB staining alone.