Quantitative susceptibility mapping for investigating brain iron deposits in amyotrophic lateral sclerosis: correlations with clinical phenotype and disease progression.

IF 2.8
Maria Agnese Pirozzi, Fabrizio Canale, Federica Di Nardo, Minoo Sharbafshaaer, Carla Passaniti, Mattia Siciliano, Mario Cirillo, Alessandro Tessitore, Gioacchino Tedeschi, Fabrizio Esposito, Francesca Trojsi
{"title":"Quantitative susceptibility mapping for investigating brain iron deposits in amyotrophic lateral sclerosis: correlations with clinical phenotype and disease progression.","authors":"Maria Agnese Pirozzi, Fabrizio Canale, Federica Di Nardo, Minoo Sharbafshaaer, Carla Passaniti, Mattia Siciliano, Mario Cirillo, Alessandro Tessitore, Gioacchino Tedeschi, Fabrizio Esposito, Francesca Trojsi","doi":"10.1080/21678421.2025.2522406","DOIUrl":null,"url":null,"abstract":"<p><p><i>Objective</i>: Perturbation of iron homeostasis is a potential key mechanism involved in neurodegeneration across many neurological disorders, including amyotrophic lateral sclerosis (ALS). We hypothesized that changes in quantitative susceptibility mapping (QSM) could capture perturbations in brain iron concentration in subgroups of ALS patients stratified by clinical phenotype and disease progression. <i>Method</i>: We enrolled 38 ALS patients (23 males - mean age: 58.7 ± 9.8), screened by clinical (ALS functional rating scale-revised, ALSFRS-R) and neuropsychological scales. Patients were a posteriori classified as fast (<i>n</i> = 16) or slow (<i>n</i> = 22) progressors. Two subgroups were also considered: pyramidal (or upper motor neuron+, UMN+) patients (<i>n</i> = 18), and patients with other phenotypes (<i>n</i> = 20). <i>Results</i>: Comparing fast vs. slow progressors, significant differences in iron deposits were observed in the left (<i>p</i> = 0.028) and right amygdala (<i>p</i> = 0.022), and in susceptibility distribution on the right hippocampus (<i>p</i> = 0.0011). Comparing UMN+ vs. other phenotypes, significant susceptibility differences emerged in the left thalamus (<i>p</i> = 0.0014) and right amygdala (<i>p</i> = 0.001). QSM changes were associated with baseline ALSFRS-R (rho = 0.36, p = 0.026) in the left paracentral cortex, and iron concentration with UMN score (rho = 0.35, <i>p</i> = 0.034). Moreover, the Edinburgh Cognitive and Behavioral ALS Screen (ECAS) was associated with iron deposits in the left thalamus (rho=-0.46, <i>p</i> = 0.0041). <i>Conclusions</i>: We confirmed that QSM alterations in extra-motor areas and subcortical regions may be distinctive hallmarks of neurodegeneration in pure/dominant UMN phenotypes of ALS. Moreover, we showed that QSM could be a valuable tool to differentiate patients with different progression rates and phenotypes, suggesting that QSM may support a prognostically useful early stratification of ALS patients.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"1-9"},"PeriodicalIF":2.8000,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Amyotrophic lateral sclerosis & frontotemporal degeneration","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1080/21678421.2025.2522406","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

Abstract

Objective: Perturbation of iron homeostasis is a potential key mechanism involved in neurodegeneration across many neurological disorders, including amyotrophic lateral sclerosis (ALS). We hypothesized that changes in quantitative susceptibility mapping (QSM) could capture perturbations in brain iron concentration in subgroups of ALS patients stratified by clinical phenotype and disease progression. Method: We enrolled 38 ALS patients (23 males - mean age: 58.7 ± 9.8), screened by clinical (ALS functional rating scale-revised, ALSFRS-R) and neuropsychological scales. Patients were a posteriori classified as fast (n = 16) or slow (n = 22) progressors. Two subgroups were also considered: pyramidal (or upper motor neuron+, UMN+) patients (n = 18), and patients with other phenotypes (n = 20). Results: Comparing fast vs. slow progressors, significant differences in iron deposits were observed in the left (p = 0.028) and right amygdala (p = 0.022), and in susceptibility distribution on the right hippocampus (p = 0.0011). Comparing UMN+ vs. other phenotypes, significant susceptibility differences emerged in the left thalamus (p = 0.0014) and right amygdala (p = 0.001). QSM changes were associated with baseline ALSFRS-R (rho = 0.36, p = 0.026) in the left paracentral cortex, and iron concentration with UMN score (rho = 0.35, p = 0.034). Moreover, the Edinburgh Cognitive and Behavioral ALS Screen (ECAS) was associated with iron deposits in the left thalamus (rho=-0.46, p = 0.0041). Conclusions: We confirmed that QSM alterations in extra-motor areas and subcortical regions may be distinctive hallmarks of neurodegeneration in pure/dominant UMN phenotypes of ALS. Moreover, we showed that QSM could be a valuable tool to differentiate patients with different progression rates and phenotypes, suggesting that QSM may support a prognostically useful early stratification of ALS patients.

研究肌萎缩侧索硬化症脑铁沉积的定量易感性图谱:与临床表型和疾病进展的相关性
目的:铁稳态的扰动是许多神经系统疾病(包括肌萎缩侧索硬化症(ALS))神经退行性变的潜在关键机制。我们假设定量易感性图谱(QSM)的变化可以捕获按临床表型和疾病进展分层的ALS患者亚组中脑铁浓度的扰动。方法:采用临床(ALS功能评定量表-修订版,ALSFRS-R)和神经心理量表筛选38例ALS患者,其中男性23例,平均年龄58.7±9.8岁。患者被后验分为快速(n = 16)或缓慢(n = 22)进展者。还考虑了两个亚组:锥体(或上运动神经元+,UMN+)患者(n = 18)和其他表型患者(n = 20)。结果:与慢速进展者相比,左杏仁核(p = 0.028)和右杏仁核(p = 0.022)的铁沉积以及右海马的易感性分布存在显著差异(p = 0.0011)。UMN+与其他表型相比,左侧丘脑(p = 0.0014)和右侧杏仁核(p = 0.001)出现了显著的易感性差异。QSM变化与左中央旁皮质ALSFRS-R基线相关(rho = 0.36, p = 0.026),铁浓度与UMN评分相关(rho = 0.35, p = 0.034)。此外,爱丁堡认知和行为ALS筛查(ECAS)与左丘脑的铁沉积有关(rho=-0.46, p = 0.0041)。结论:我们证实,运动外区和皮层下区域的QSM改变可能是ALS纯/显性UMN表型中神经退行性变的独特标志。此外,我们发现QSM可能是区分不同进展率和表型的患者的有价值的工具,这表明QSM可能支持ALS患者的预后有用的早期分层。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
自引率
0.00%
发文量
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信