Department of Neurology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
Department of Molecular Neurology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
Ann Clin Transl Neurol. 2023 Jul;10(7):1230-1238. doi: 10.1002/acn3.51818. Epub 2023 May 31.
Adrenoleukodystrophy (ALD) has a poor prognosis when it progresses to the cerebral form (CALD). The aim of this study is to investigate whether cerebrospinal fluid (CSF) neurofilament light chain (cNfL) is a sensitive biomarker for detecting CALD and assessing response to hematopoietic stem cell transplantation (HSCT).
We conducted a cross-sectional study of 41 male ALD patients. The cNfL levels in patients with the cerebral form of ALD (CALD) or the cerebello-brainstem form of ALD were compared with those in patients with adrenomyeloneuropathy (AMN). The correlation between cNfL levels and MRI-based Loes severity scores was investigated. A longitudinal analysis was performed on patients who underwent multiple CSF examinations.
The cNfL levels in 22 patients with CALD were significantly higher than those in 14 patients with AMN (median, 5545 vs. 1490 pg/mL; p < 0.001). The cutoff cNfL level of 1930 pg/mL showed good sensitivity (95.5%) and specificity (85.7%) for distinguishing CALD from AMN. The cNfL levels were positively correlated with Loes scores (p < 0.001). The cNfL levels in three AMN patients who later converted to CALD increased above the cutoff level during the conversion period, while the cNfL levels in four patients who remained in AMN were consistently below the cutoff. In 10 ALD patients who underwent HSCT, their cNfL levels decreased 3-24 months after HSCT. Two patients whose cNfL increased after HSCT showed deterioration in cognitive functions.
The cNfL level is useful for evaluating the disease activities of ALD and the response to HSCT.
肾上腺脑白质营养不良（ALD）进展为脑型（CALD）时预后较差。本研究旨在探讨脑脊液（CSF）神经丝轻链（cNfL）是否可作为检测 CALD 和评估造血干细胞移植（HSCT）反应的敏感生物标志物。
我们进行了一项横断面研究，共纳入 41 名男性 ALD 患者。比较了 CALD 患者和肾上腺脑桥小脑病（AMN）患者的 CSF cNfL 水平，同时还研究了 cNfL 水平与基于 MRI 的 Loes 严重程度评分之间的相关性。对接受多次 CSF 检查的患者进行了纵向分析。
22 例 CALD 患者的 cNfL 水平明显高于 14 例 AMN 患者（中位数，5545 与 1490 pg/mL；p<0.001）。1930 pg/mL 的 cNfL 截断值对区分 CALD 和 AMN 具有良好的敏感性（95.5%）和特异性（85.7%）。cNfL 水平与 Loes 评分呈正相关（p<0.001）。3 例后来转化为 CALD 的 AMN 患者在转化期内 cNfL 水平升高至截断值以上，而 4 例仍处于 AMN 的患者 cNfL 水平持续低于截断值。10 例接受 HSCT 的 ALD 患者在 HSCT 后 3-24 个月其 cNfL 水平下降。2 例 HSCT 后 cNfL 升高的患者认知功能恶化。
cNfL 水平可用于评估 ALD 的疾病活动度和 HSCT 反应。
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