Qiu Haishan, Hu Manshi, Jiang Chao, Wu Jiale, Huang Zihuan, Liang Jiahui, Sha Runhua, Zeng Wenting, Wu Chao, Chu Jianping, Zhao Jing
Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, PR China.
Department of Medical Imaging, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, PR China.
Eur J Neurol. 2025 Apr;32(4):e70127. doi: 10.1111/ene.70127.
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.
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.
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).
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.
3型脊髓小脑共济失调（SCA3）是一种罕见的遗传性神经退行性疾病。人们对SCA3的铁分布了解甚少，然而定量磁化率成像（QSM）在SCA3中很少被使用。
我们前瞻性地研究了2018年5月至2021年1月招募的SCA3患者（19名症状前患者和41名症状性患者）以及37名健康对照者（HCs）的QSM。对各组的磁化率进行横断面比较，并探讨脑铁沉积改变与临床症状、神经丝轻链（Nfl）以及双侧皮质脊髓束和小脑脚各向异性分数之间的关联。对12名SCA3参与者进行了至少一年的随访。
与HCs相比，在症状前SCA3患者中观察到双侧黑质的磁化率显著增加。大多数幕上核以及右侧齿状核在症状期的磁化率高于症状前期，并且部分与症状严重程度、病程以及受损的小脑脚相关（p < 0.05），但与Nfl无关（p > 0.05）。左侧黑质（SN）在识别症状前（AUC = 0.904）和症状性SCA3（AUC = 0.938）方面显示出最高的诊断效能。纵向研究也证实了左侧黑质的显著变化（p < 0.01）。
我们的活体QSM证据表明SCA3患者脑铁沉积具有疾病特异性模式。脑铁沉积异常是SCA3发生和发展的早期事件。左侧黑质可能是该疾病起始和发展的关键部位。
