Quantitative susceptibility mapping of dentate nucleus iron in SCA6 and SCA31: comparison with pathological findings

Spinocerebellar ataxia type 6 (SCA6) and 31 (SCA31) exhibit similar clinical and radiological features and have traditionally been distinguishable only through genetic testing. We focused on iron deposition in the cerebellar dentate nucleus (DN) to differentiate these diseases, referencing corresponding pathological findings.

Using quantitative susceptibility mapping (QSM), DN susceptibility was measured in 32 patients with SCA6, 31 with SCA31, and 37 controls, and the values were compared among groups. Correlations between susceptibility and disease duration or Scale for the Assessment and Rating of Ataxia (SARA) scores were also evaluated. In separate autopsy cases, Berlin blue and anti-ferritin immunostaining were performed on the DN in five SCA6 cases, one SCA31 case, and three controls.

Susceptibility was significantly lower in patients with SCA6 than in those with SCA31 or controls. In SCA6, susceptibility inversely correlated with disease duration, whereas no such correlations were observed in SCA31. In contrast, no significant correlation was noted between susceptibility and SARA scores in either SCA6 or SCA31. Pathological findings showed absent ferritin staining in SCA6, strong staining in controls, and intermediate staining in SCA31. Berlin blue staining was negative in all groups.

Reduced DN susceptibility in SCA6 reflects ferritin loss, distinguishing it from SCA31. Assessing DN susceptibility using QSM or SWI may provide useful imaging markers to complement the diagnosis of SCA6 and SCA31.