Potential markers for sample size estimations in hereditary spastic paraplegia type 5.
Potential markers for sample size estimations in hereditary spastic paraplegia type 5.
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遗传性痉挛性截瘫 5 型样本量估计的潜在标志物
DOI：
10.1186/s13023-021-02014-w
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发表时间：
2021-09-19
影响因子：
3.7
通讯作者：
Fu Y
中科院分区：
文献类型：
--
作者：
Lin Q;Liu Y;Ye Z;Hu J;Cai W;Weng Q;Chen WJ;Wang N;Cao D;Lin Y;Fu Y
目的通过研究遗传性痉挛性截瘫5型（SPG 5）的临床、脑脊液（CSF）和磁共振成像（MRI）特征，寻找潜在的生物标志物，以评估SPG 5的治疗效果。我们进行了一项横断面研究，比较SPG 5患者与年龄和性别匹配的健康对照者，他们接受了脊髓（C1-T9）和大脑的常规和定量MRI技术。SPG 5患者还接受了临床状态和CSF生物标志物（27-羟基胆固醇、神经丝光）评估。我们确定了一组具有标准化效应量的标记物（|不|> 0.5）来估计疾病进展的样本量（疾病持续时间> 14年vs. ≤ 14年）。入组了17例经遗传学证实的SPG 5患者（11例男性，6例女性;年龄范围：13-49岁;中位病程：14年）。与健康对照组相比，SPG 5患者的脊髓总面积（SCA）减少，特别是在胸部水平（颈部水平：12-27%;胸部水平41-60%）。相对于对照组，患者没有表现出脑信号异常或萎缩的显著改变。共选择了10个替代标志物，并在T9（n = 22）测量SCA时达到最小样本量，远低于使用临床残疾评估（n = 124）时所需的样本量。SPG 5患者表现出明显的脊髓萎缩MRI特征，但无明显的脑改变。我们的发现支持T9水平脊髓测量作为SPG 5临床试验的潜在终点。试用注册ClinicalTrials.gov，NCT 04006418。2019年7月5日注册，https://clinicaltrials.gov/ct2/show/NCT04006418? term= NCT04006418 & draw =2&rank=1。在线版本包含补充材料，可在10.1186/s13023-021-02014-w获得。
Aim to identify potential biomarkers to assess therapeutic efficacy for hereditary spastic paraplegias type 5 (SPG5) by investigating the clinical, cerebrospinal fluid (CSF) and magnetic resonance imaging (MRI) features. We performed a cross-sectional study to compare SPG5 patients with age- and sex-matched healthy controls who underwent conventional and quantitative MRI techniques of spinal cord (C1-T9) and brain. SPG5 patients also underwent assessment for clinical status and CSF biomarkers (27-hydroxycholesterol, neurofilament light). We identified a set of markers with standardized effect sizes (|t|> 0.5) to estimate sample sizes for disease progression (disease duration > 14 years vs. ≤ 14 years). Seventeen genetically confirmed SPG5 patients (11 men, 6 women; age range, 13–49 years; median disease duration, 14 years) were enrolled. Compared to healthy controls, the total spinal cord area (SCA) of SPG5 patients was reduced particularly at the thoracic levels (cervical levels: 12–27%; thoracic levels 41–60%). Patients did not show significant alterations of brain signal abnormalities or atrophy relative to controls. A total of 10 surrogate markers were selected and a minimum sample size was achieved with the measurement of SCA on T9 (n = 22) much less that what would be required if using clinical disability assessment (n = 124). SPG5 patients showed distinct MRI features of spinal cord atrophy without significant brain alterations. Our finding supports the measurements of spinal cord on T9 level as potential endpoint for SPG5 clinical trials. Trial registration ClinicalTrials.gov, NCT04006418. Registered 05 July 2019, https://clinicaltrials.gov/ct2/show/NCT04006418?term=NCT04006418&draw=2&rank=1. The online version contains supplementary material available at 10.1186/s13023-021-02014-w.
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影响因子：
158.5
作者：
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通讯作者：
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影响因子：
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