Degeneration of the inferior olive in spinocerebellar ataxia 6 may depend on disease duration: Report of two autopsy cases and statistical analysis of autopsy cases reported to date

Abstract

This report concerns a clinicopathological study of two autopsied patients with spinocerebellar ataxia 6 (SCA6), and a statistical analysis between neuronal loss of the inferior olive and disease duration of 15 SCA6 autopsy cases reported to date, including the two cases reported in this study. Cases 1 and 2 came from independent Japanese families. Case 1 developed gait disturbance at age 35 years and died at age 78 years; she had a CAG-repeat expansion of the SCA6 gene (25/13). Case 2 presented with gait disturbance at age 68 years and died at age 78 years; he had an expanded CAG-repeat of the SCA6 gene (22/13). Neuropathological examination of both cases disclosed not only neuronal loss of the Purkinje cells and inferior olive, but also some unnoticed features, including cactus-like expansion of the dendrite of Purkinje cells and relative preservation of Golgi cells in the granular layer of the cerebellum. Exploratory statistical analysis between 11 SCA6 autopsy cases with neuronal loss in the inferior olive (average disease duration: 27 years) and four SCA6 autopsy cases without neuronal loss in the olive (average disease duration: 14.5 years) was investigated by Kaplan-Meier estimates of survival and log-rank test, retrospectively. Kaplan-Meier estimates of survival revealed an obvious difference between the two groups. Survival of 10 years after the disease onset was 90.9% in the former 11 SCA6 autopsy cases, but was 50% in the latter four SCA6 autopsy cases. Furthermore, a log-rank test on the two groups disclosed a significant difference (P=0.0450). We postulate that the neuronal loss of the inferior olive in SCA6 may depend on disease duration.

Distribution of cerebello‐olivary degeneration in idiopathic late cortical cerebellar atrophy: Clinicopathological study of four autopsy cases

“…In contrast, in case 3, which did not show distinct neuronal loss in the inferior olivary nucleus, the duration of illness was shorter than in other cases, the granular cell loss and narrowing of the molecular layer was mild and there were few lesions belonging to Grade 3 or more. These findings suggest that the lesion of the inferior olivary nucleus is related to the level of cerebellar cortical lesion, especially changes of the granular cell and molecular layer and to the period of suffering from the disease as well as SCA6 18 . As mentioned above, our study disclosed that cerebello‐olivary degeneration of idiopathic LCCA has a striking resemblance to that of SCA6 13–16 .…”

The wide clinical spectrum and nigrostriatal dopaminergic damage in spinocerebellar ataxia type 6

“…A neuropathological examination by Gomez and colleagues12 showed that the substantia nigra and striatum had no significant cell loss. Tsuchiya and colleagues13 also reported that neuronal loss was not evident in these areas, and post-mortem studies by Takahashi and colleagues14 and Tashiro and colleagues15 produced similar findings. Furthermore, dopamine transporter (DAT) positron emission tomography using [ 11 C]d-threo-methylphenidate revealed that SCA6 has normal binding potential16 but Khan and colleagues,10 using [ 18 F]-dopa positron emission tomography, reported that the nigrostriatal dopaminergic system is involved in SCA6.…”

Chromosome 16q22.1‐linked autosomal dominant cerebellar ataxia: An autopsy case report with some new observations on cerebellar pathology

“…Tsuchiya et al. stated that in SCA 6, degeneration of the inferior olivary nucleus depends on disease duration 16 . The clinical disease duration in the case of Owada et al.…”