Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano.
Department of Pathophysiology and Transplantation, 'Dino Ferrari' Center, Università degli Studi di Milano, Milan, Italy.
Curr Opin Neurol. 2019 Oct;32(5):747-757. doi: 10.1097/WCO.0000000000000744.
The diagnosis of amyotrophic lateral sclerosis (ALS) still relies mainly on clinical criteria. In present review we will provide an overview of neurochemical ALS biomarkers, which are in the most advanced position on the way towards inclusion into the clinical work-up.
The field of ALS neurology still lacks a neurochemical marker for routine clinical use. However, this is urgently needed, because it would help in diagnosis, prognostic stratification, and monitoring of drug response. Despite this lack of a routinely used biomarker, in the last decade significant progress has been made in the field. In particular, two molecules have been extensively studied - the light chain and the phosphorylated form of the heavy chain of neurofilaments, NFL and pNFH, respectively - which have demonstrated a high diagnostic performance and promising prognostic value and are therefore ready to be introduced into the clinical scenario. On the other hand, we still lack a neurochemical cerebrospinal fluid or blood biomarker reflecting TDP-43 pathology.
Neurofilaments seem to be ready for clinical use in the early and differential diagnosis of ALS. We also highlight still unresolved issues which deserve further investigation.
肌萎缩侧索硬化症（ALS）的诊断主要依赖于临床标准。在本次综述中，我们将概述神经化学 ALS 生物标志物，这些标志物在纳入临床评估方面处于最先进的地位。
ALS 神经病学领域仍缺乏常规临床应用的神经化学标志物。然而，这是非常需要的，因为它有助于诊断、预后分层和药物反应监测。尽管缺乏常规使用的生物标志物，但在过去十年中，该领域取得了重大进展。特别是两种分子得到了广泛的研究 - 神经丝的轻链和重链的磷酸化形式，分别为 NFL 和 pNFH - 它们表现出了较高的诊断性能和有前途的预后价值，因此准备引入临床。另一方面，我们仍然缺乏反映 TDP-43 病理学的神经化学脑脊液或血液生物标志物。
神经丝似乎已经准备好在 ALS 的早期和鉴别诊断中进行临床应用。我们还强调了一些仍未解决的问题，这些问题值得进一步研究。
