Research Institute of Neuromuscular and Neurodegenerative Disease, Department of Neurology, Qilu Hospital, Shandong University, West Wenhua Street No.107, 250012, Jinan, China.
School of Clinical Medicine, Shandong Second Medical University, Weifang, China.
Fluids Barriers CNS. 2024 Apr 17;21(1):36. doi: 10.1186/s12987-024-00536-6.
Using in vivo neuroimaging techniques, growing evidence has demonstrated that the choroid plexus (CP) volume is enlarged in patients with several neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. However, although animal and postmortem findings suggest that CP abnormalities are likely important pathological mechanisms underlying amyotrophic lateral sclerosis (ALS), the third most common neurodegenerative disease, no available study has been conducted to thoroughly assess CP abnormalities and their clinical relevance in vivo in ALS patients to date. Thus, we aimed to determine whether in vivo CP enlargement may occur in ALS patients. We also aimed to identify the relationships of CP volume with clinical disabilities and blood-CSF barrier (BCSFB) permeability in ALS patients.
In this retrospective study, based on structural MRI data, CP volume was assessed using a Gaussian mixture model and underwent further manual correction in 155 ALS patients and 105 age- and sex-matched HCs from October 2021 to April 2023. The ALS Functional Rating Scale-Revised (ALSFRS-R) was used to assess clinical disability. The CSF/serum albumin quotient (Qalb) was used to assess BCSFB permeability. Moreover, all the ALS patients completed genetic testing, and according to genetic testing, the ALS patients were further divided into genetic ALS subgroup and sporadic ALS subgroup.
We found that compared with HCs, ALS patients had a significantly higher CP volume (p < 0.001). Moreover, compared with HCs, CP volume was significantly increased in both ALS patients with and without known genetic mutations after family-wise error correction (p = 0.006 and p < 0.001, respectively), while there were no significant differences between the two ALS groups. Furthermore, the CP volume was significantly correlated with the ALSFRS-r score (r = -0.226; p = 0.005) and the Qalb (r = 0.479; p < 0.001) in ALS patients.
Our study first demonstrates CP enlargement in vivo in ALS patients, and continues to suggest an important pathogenetic role for CP abnormalities in ALS. Moreover, assessing CP volume is likely a noninvasive and easy-to-implement approach for screening BCSFB dysfunction in ALS patients.
使用活体神经影像学技术，越来越多的证据表明脉络丛（CP）体积在包括阿尔茨海默病和帕金森病在内的几种神经退行性疾病患者中增大。然而，尽管动物和尸检研究表明 CP 异常可能是肌萎缩侧索硬化症（ALS）的重要病理机制，ALS 是第三大常见的神经退行性疾病，但迄今为止，尚无研究全面评估 ALS 患者体内 CP 异常及其与临床相关性。因此，我们旨在确定活体 CP 增大是否可能发生在 ALS 患者中。我们还旨在确定 CP 体积与 ALS 患者临床残疾和血脑屏障（BCSFB）通透性的关系。
在这项回顾性研究中，基于结构 MRI 数据，使用高斯混合模型评估 CP 体积，并在 2021 年 10 月至 2023 年 4 月期间对 155 名 ALS 患者和 105 名年龄和性别匹配的 HC 进行进一步的手动校正。使用 ALS 功能评定量表修订版（ALSFRS-R）评估临床残疾。CSF/血清白蛋白商（Qalb）用于评估 BCSFB 通透性。此外，所有 ALS 患者均完成了基因检测，根据基因检测结果，ALS 患者进一步分为遗传 ALS 亚组和散发性 ALS 亚组。
我们发现，与 HC 相比，ALS 患者的 CP 体积明显更高（p<0.001）。此外，在经过家族性错误校正后，与 HC 相比，无论是否具有已知基因突变，ALS 患者的 CP 体积均显著增加（p=0.006 和 p<0.001，分别），而两组 ALS 患者之间无显著差异。此外，CP 体积与 ALS 患者的 ALSFRS-r 评分（r=-0.226；p=0.005）和 Qalb（r=0.479；p<0.001）显著相关。
我们的研究首次在 ALS 患者中体内证明 CP 增大，并进一步表明 CP 异常在 ALS 中具有重要的发病机制作用。此外，评估 CP 体积可能是筛选 ALS 患者 BCSFB 功能障碍的一种非侵入性且易于实施的方法。
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