Federico Verde1, Vincenzo Silani1,2, Markus Otto3. 1. Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano. 2. Department of Pathophysiology and Transplantation, 'Dino Ferrari' Center, Università degli Studi di Milano, Milan, Italy. 3. Department of Neurology, University of Ulm, Ulm, Germany.
Abstract
PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: 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.
PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: 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.
Authors: Stephen A Goutman; Orla Hardiman; Ammar Al-Chalabi; Adriano Chió; Masha G Savelieff; Matthew C Kiernan; Eva L Feldman Journal: Lancet Neurol Date: 2022-03-22 Impact factor: 59.935
Authors: Simon Witzel; Felix Frauhammer; Markus Otto; Albert C Ludolph; Petra Steinacker; David Devos; Pierre-François Pradat; Vincent Meininger; Steffen Halbgebauer; Patrick Oeckl; Joachim Schuster; Simon Anders; Johannes Dorst Journal: Transl Neurodegener Date: 2021-08-26 Impact factor: 8.014