Department of Paediatric Neurology, Amsterdam Leukodystrophy Center, Emma Children's Hospital, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands.
Department of Neurology, OLVG Hospital, Amsterdam, The Netherlands.
Ann Clin Transl Neurol. 2020 Nov;7(11):2127-2136. doi: 10.1002/acn3.51188. Epub 2020 Oct 13.
To explore the potential of neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) as biomarkers of spinal cord degeneration in adrenoleukodystrophy, as objective treatment-outcome parameters are needed.
Plasma NfL and GFAP levels were measured in 45 male and 47 female ALD patients and compared to a reference cohort of 73 healthy controls. For male patients, cerebrospinal fluid (CSF) samples (n = 33) and 1-year (n = 39) and 2-year (n = 18) follow-up data were also collected. Severity of myelopathy was assessed with clinical parameters: Expanded Disability Status Scale (EDSS), Severity Scoring system for Progressive Myelopathy (SSPROM), and timed up-and-go.
NfL and GFAP levels were higher in male (P < 0.001, effect size (partial ƞ ) NfL = 0.49, GFAP = 0.13) and female (P < 0.001, effect size NfL = 0.19, GFAP = 0.23) patients compared to controls; levels were higher in both symptomatic and asymptomatic patients. In male patients, NfL levels were associated with all three clinical parameters of severity of myelopathy (EDSS, SSPROM, and timed up-and go), while GFAP in male and NfL and GFAP in female patients were not. Changes in clinical parameters during follow-up did not correlate with (changes in) NfL or GFAP levels. Plasma and CSF NfL were strongly correlated (r = 0.60, P < 0.001), but plasma and CSF GFAP were not (r = 0.005, P = 0.98).
Our study illustrates the potential of plasma NfL as biomarker of spinal cord degeneration in adrenoleukodystrophy, which was superior to plasma GFAP in our cohort.
探索神经丝轻链（NfL）和胶质纤维酸性蛋白（GFAP）作为肾上腺脑白质营养不良（ALD）脊髓退化的生物标志物的潜力，因为需要客观的治疗效果参数。
测量了 45 名男性和 47 名女性 ALD 患者以及 73 名健康对照者的血浆 NfL 和 GFAP 水平。对于男性患者，还收集了脑脊液（CSF）样本（n=33）和 1 年（n=39）和 2 年（n=18）的随访数据。采用临床参数评估脊髓病的严重程度：扩展残疾状况量表（EDSS）、进行性脊髓病严重程度评分系统（SSPROM）和计时起立行走。
与对照组相比，男性（P<0.001，NfL 的效应大小（部分ƞ）为 0.49，GFAP 为 0.13）和女性（P<0.001，NfL 的效应大小为 0.19，GFAP 为 0.23）患者的 NfL 和 GFAP 水平均较高；在有症状和无症状患者中，水平均较高。在男性患者中，NfL 水平与脊髓病严重程度的所有三个临床参数（EDSS、SSPROM 和计时起立行走）相关，而男性和女性患者的 GFAP 以及 NfL 和 GFAP 则不相关。随访期间临床参数的变化与 NfL 或 GFAP 水平的变化无关。血浆和 CSF NfL 之间具有很强的相关性（r=0.60，P<0.001），而血浆和 CSF GFAP 之间则没有相关性（r=0.005，P=0.98）。
我们的研究表明，血浆 NfL 有可能成为肾上腺脑白质营养不良脊髓退化的生物标志物，在我们的队列中优于血浆 GFAP。
