对显性亨廷顿氏病前期和过渡期神经丝蛋白轻链动态的 14 年纵向研究。

IF 4.8 2区 医学 Q1 CLINICAL NEUROLOGY
Journal of Neurology Pub Date : 2024-12-01 Epub Date: 2024-10-03 DOI:10.1007/s00415-024-12700-x
Z J Voysey, N E Owen, J A Holbrook, M Malpetti, C Le Draoulec, L R B Spindler, A O G Goodman, A S Lazar, R A Barker
{"title":"对显性亨廷顿氏病前期和过渡期神经丝蛋白轻链动态的 14 年纵向研究。","authors":"Z J Voysey, N E Owen, J A Holbrook, M Malpetti, C Le Draoulec, L R B Spindler, A O G Goodman, A S Lazar, R A Barker","doi":"10.1007/s00415-024-12700-x","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Growing evidence supports the value of neurofilament light (NfL) as a prognostic biomarker in premanifest Huntington's disease (HD). To date, however, there has been no longitudinal study exceeding 3 years examining either its serial dynamics or predictive power in HD. We aimed to conduct the first such study.</p><p><strong>Methods: </strong>Serum NfL was sampled using ultrasensitive immunoassay at four timepoints across a 14-year period in a cohort of HD gene carriers (n = 21) and controls (n = 14). Gene carriers were premanifest at baseline. Clinical features of HD were evaluated by Unified Huntington's Disease Rating Scale (UHDRS TMS), Montreal Cognitive Assessment (MoCA), Trail A/B task, Symbol Digit Modalities Task and semantic/phonemic fluency tasks.</p><p><strong>Results: </strong>14/21 HD gene carriers converted to prodromal or manifest disease by the final timepoint (\"converters\"). At baseline and each subsequent timepoint, NfL levels were higher in converters than in non-converters and controls (p = < 0.001-0.03, η<sub>p</sub><sup>2</sup> = 0.25-0.66). The estimated rate of change in NfL was higher in converters than in non-converters (p = 0.03) and controls (p = 0.001). Baseline NfL was able to discriminate converters from non-converters (area under curve = 1.000, p = 0.003). A higher rate of change in NfL was predictive of more severe motor (UHDRS-TMS p = 0.007, β = 0.711, R<sup>2</sup> = 0.468) and cognitive deficits (MoCA p = 0.007, β = - 0.798, R<sup>2</sup> = 0.604; Trail B, p = 0.007, β = 0.772, R<sup>2</sup> = 0.567; phonemic fluency p = 0.035, β = - 0.632, R<sup>2</sup> = 0.345).</p><p><strong>Conclusions: </strong>Our data suggest that (1) NfL longitudinal dynamics in premanifest/transitional HD are non-constant; rising faster in those closer to disease onset, and (2) NfL can identify individuals at risk of conversion to manifest disease and predict clinical trajectory, > 10 years from disease onset.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":" ","pages":"7572-7582"},"PeriodicalIF":4.8000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"A 14-year longitudinal study of neurofilament light chain dynamics in premanifest and transitional Huntington's disease.\",\"authors\":\"Z J Voysey, N E Owen, J A Holbrook, M Malpetti, C Le Draoulec, L R B Spindler, A O G Goodman, A S Lazar, R A Barker\",\"doi\":\"10.1007/s00415-024-12700-x\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Growing evidence supports the value of neurofilament light (NfL) as a prognostic biomarker in premanifest Huntington's disease (HD). To date, however, there has been no longitudinal study exceeding 3 years examining either its serial dynamics or predictive power in HD. We aimed to conduct the first such study.</p><p><strong>Methods: </strong>Serum NfL was sampled using ultrasensitive immunoassay at four timepoints across a 14-year period in a cohort of HD gene carriers (n = 21) and controls (n = 14). Gene carriers were premanifest at baseline. Clinical features of HD were evaluated by Unified Huntington's Disease Rating Scale (UHDRS TMS), Montreal Cognitive Assessment (MoCA), Trail A/B task, Symbol Digit Modalities Task and semantic/phonemic fluency tasks.</p><p><strong>Results: </strong>14/21 HD gene carriers converted to prodromal or manifest disease by the final timepoint (\\\"converters\\\"). At baseline and each subsequent timepoint, NfL levels were higher in converters than in non-converters and controls (p = < 0.001-0.03, η<sub>p</sub><sup>2</sup> = 0.25-0.66). The estimated rate of change in NfL was higher in converters than in non-converters (p = 0.03) and controls (p = 0.001). Baseline NfL was able to discriminate converters from non-converters (area under curve = 1.000, p = 0.003). A higher rate of change in NfL was predictive of more severe motor (UHDRS-TMS p = 0.007, β = 0.711, R<sup>2</sup> = 0.468) and cognitive deficits (MoCA p = 0.007, β = - 0.798, R<sup>2</sup> = 0.604; Trail B, p = 0.007, β = 0.772, R<sup>2</sup> = 0.567; phonemic fluency p = 0.035, β = - 0.632, R<sup>2</sup> = 0.345).</p><p><strong>Conclusions: </strong>Our data suggest that (1) NfL longitudinal dynamics in premanifest/transitional HD are non-constant; rising faster in those closer to disease onset, and (2) NfL can identify individuals at risk of conversion to manifest disease and predict clinical trajectory, > 10 years from disease onset.</p>\",\"PeriodicalId\":16558,\"journal\":{\"name\":\"Journal of Neurology\",\"volume\":\" \",\"pages\":\"7572-7582\"},\"PeriodicalIF\":4.8000,\"publicationDate\":\"2024-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Neurology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s00415-024-12700-x\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/10/3 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Neurology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00415-024-12700-x","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/10/3 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0

摘要

背景:越来越多的证据表明,神经丝光(NfL)可作为显现前亨廷顿氏病(HD)的预后生物标志物。然而,迄今为止,还没有一项超过 3 年的纵向研究对 NfL 在 HD 中的序列动态或预测能力进行研究。我们的目标是开展第一项此类研究:方法:使用超灵敏免疫测定法,在 HD 基因携带者(21 人)和对照组(14 人)的 14 年间的四个时间点采集血清 NfL 样本。基因携带者基线为发病前。HD的临床特征通过统一亨廷顿氏病评分量表(UHDRS TMS)、蒙特利尔认知评估(MoCA)、径迹A/B任务、符号数字模型任务和语义/语音流畅性任务进行评估:14/21名HD基因携带者在最后一个时间点转为前驱或显性疾病("转换者")。在基线和随后的每个时间点,转换者的 NfL 水平均高于未转换者和对照组(p = p2 = 0.25-0.66)。转换者的 NfL 估计变化率高于非转换者(p = 0.03)和对照组(p = 0.001)。基线 NfL 能够区分转换者和非转换者(曲线下面积 = 1.000,p = 0.003)。较高的 NfL 变化率可预测更严重的运动障碍(UHDRS-TMS p = 0.007, β = 0.711, R2 = 0.468)和认知障碍(MoCA p = 0.007, β = - 0.798, R2 = 0.604; Trail B, p = 0.007, β = 0.772, R2 = 0.567; phonemic fluency p = 0.035, β = - 0.632, R2 = 0.345):我们的数据表明:(1) NfL 在显现前/过渡型 HD 中的纵向动态变化是非恒定的;在更接近发病期的人群中上升更快;(2) NfL 可以识别有转化为显现疾病风险的个体,并预测距发病期 > 10 年的临床轨迹。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
A 14-year longitudinal study of neurofilament light chain dynamics in premanifest and transitional Huntington's disease.

Background: Growing evidence supports the value of neurofilament light (NfL) as a prognostic biomarker in premanifest Huntington's disease (HD). To date, however, there has been no longitudinal study exceeding 3 years examining either its serial dynamics or predictive power in HD. We aimed to conduct the first such study.

Methods: Serum NfL was sampled using ultrasensitive immunoassay at four timepoints across a 14-year period in a cohort of HD gene carriers (n = 21) and controls (n = 14). Gene carriers were premanifest at baseline. Clinical features of HD were evaluated by Unified Huntington's Disease Rating Scale (UHDRS TMS), Montreal Cognitive Assessment (MoCA), Trail A/B task, Symbol Digit Modalities Task and semantic/phonemic fluency tasks.

Results: 14/21 HD gene carriers converted to prodromal or manifest disease by the final timepoint ("converters"). At baseline and each subsequent timepoint, NfL levels were higher in converters than in non-converters and controls (p = < 0.001-0.03, ηp2 = 0.25-0.66). The estimated rate of change in NfL was higher in converters than in non-converters (p = 0.03) and controls (p = 0.001). Baseline NfL was able to discriminate converters from non-converters (area under curve = 1.000, p = 0.003). A higher rate of change in NfL was predictive of more severe motor (UHDRS-TMS p = 0.007, β = 0.711, R2 = 0.468) and cognitive deficits (MoCA p = 0.007, β = - 0.798, R2 = 0.604; Trail B, p = 0.007, β = 0.772, R2 = 0.567; phonemic fluency p = 0.035, β = - 0.632, R2 = 0.345).

Conclusions: Our data suggest that (1) NfL longitudinal dynamics in premanifest/transitional HD are non-constant; rising faster in those closer to disease onset, and (2) NfL can identify individuals at risk of conversion to manifest disease and predict clinical trajectory, > 10 years from disease onset.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Journal of Neurology
Journal of Neurology 医学-临床神经学
CiteScore
10.00
自引率
5.00%
发文量
558
审稿时长
1 months
期刊介绍: The Journal of Neurology is an international peer-reviewed journal which provides a source for publishing original communications and reviews on clinical neurology covering the whole field. In addition, Letters to the Editors serve as a forum for clinical cases and the exchange of ideas which highlight important new findings. A section on Neurological progress serves to summarise the major findings in certain fields of neurology. Commentaries on new developments in clinical neuroscience, which may be commissioned or submitted, are published as editorials. Every neurologist interested in the current diagnosis and treatment of neurological disorders needs access to the information contained in this valuable journal.
×
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:481959085
Book学术官方微信