Altered Brain Iron Depositions of Spinocerebellar Ataxia Type 3: From Pre-Symptomatic to Symptomatic Stage.

BACKGROUND

Spinocerebellar ataxia type 3 (SCA3) is a rare hereditary neurodegeneration disease. The iron distribution of SCA3 is poorly understood, yet quantitative susceptibility mapping (QSM) has rarely been used in SCA3.

METHODS

We prospectively investigated QSM of SCA3 (19 pre-symptomatic and 41 symptomatic) and 37 healthy controls (HCs) recruited from 2018.05 to 2021.01. Group susceptibility was cross-sectionally compared, and the associations between altered brain iron deposition and clinical symptoms, neurofilament light chain (Nfl), and fractional anisotropy of the bilateral corticospinal tracts and cerebellar peduncles were explored. 12 SCA3 participants were followed for at least a year.

RESULTS

Compared to HCs, bilateral SN were observed with significantly increased susceptibility in pre-symptomatic SCA3. Most of the supratentorial nuclei and the right dental nucleus had increased susceptibility in symptomatic than in pre-symptomatic stage and were partially correlated with symptomatic severity, disease duration, and damaged cerebellar peduncles (p < 0.05) but not Nfl (p > 0.05). The left substantia nigra (SN) demonstrated the highest diagnostic efficacy in identifying pre- (AUC = 0.904) and symptomatic SCA3 (AUC = 0.938). The longitudinal study also confirmed the significant change in the left SN (p < 0.01).

CONCLUSIONS

Our in vivo QSM evidence demonstrates disease-specific patterns for brain iron depositions in SCA3. Brain iron deposition abnormality is an early event of the SCA3's occurrence and development. The left SN might be a critical site for the disease's start and development.