[7-9] In Table 1, the clinicopathological findings of our case are compared with the six previously reported cases of FALS with the I113T SOD1 mutation.[10-14] The clinical manifestation of FALS with the I113T mutation seems quite variable. Three cases, including ours, had no family history of neuromuscular Seliciclib mouse disease. The initial symptoms were limb weakness in all cases, and no bulbar sign as the initial symptom was reported. The duration of disease was variable: relatively short, 1–3 years, in six cases, and relatively long,

over 10 years, in one case. The disease duration of our case was 7 months, the shortest among the previous reports. In addition to the pyramidal tracts, the posterior column and spinocerebellar tracts also showed evidence of degeneration in FALS with the I113T mutation. However, there were some

variations in pathological alterations from case to case. There were two cases without obvious degeneration of the posterior column, including our case. Five cases had no pyramidal tract degeneration or relatively mild degeneration compared with that in the posterior column or spinocerebellar tract. Neuronal cell loss was earlier reported to occur not only in the spinal cord lower motor neurons but also in Betz cells and other neurons in the brain stem motor nuclei and Clarke’s nucleus.[10, 12-14] As for the inclusions seen in motor neurons, CIs were observed only in Betz cells and the anterior horn cells in our case. The immunohistochemical features H 89 cell line of our case, that is, immunoreactivity for neurofilaments, partial immunoreactivity for ubiquitin, faint or no immunoreactivity for SOD1, were fully consistent with the previous reports. CIs are often observed in the cases with the autosomal-dominant form of FALS caused by mutations of the SOD1 gene. Five

different mutations have been reported, resulting in the following amino acid substitutions: A4T,[16] A4V,[17-19] H46A,[20] H48G,[21] and I113T.[10, 12-14] FALS cases with both CIs and LBHIs have been previously reported (five cases involving A4T,[16] A4V[17-19] or H48G,[21] Table 2). mafosfamide Differing from our case, degeneration of the posterior column was described in these cases. On the other hand, all cases, including ours, were of the adult-onset type and had short disease duration of less than 1 year. Our case also had NFTs, which are not usually seen in either SALS or FALS;[22] although they are well recognized in Guamanian ALS[23] and have been described in cases of ALS occurring as a delayed complication of encephalitis lethargica.[24] These NFTs were positive for tau. There has been just one other case of FALS with tau-positive NFTs, described by Orrell et al.[11] It had the same mutation but a much longer clinical course, and thus was different from ours. Neither case had parkinsonism or dementia. The distributions of NFTs and threads were similar to each other, and these structures were not observed in the cerebral cortex.