Plasma neurofilament light chain as a potential biomarker in Charcot‐Marie‐Tooth disease

Abstract

Background and purpose Charcot‐Marie‐Tooth (CMT) disease is a chronic, slowly progressing disorder. The lack of specific disease progression biomarkers limits the execution of clinical trials. However, neurofilament light chain (NfL) has been suggested as a potential biomarker for peripheral nervous system disorders. Methods Ninety‐six CMT disease patients and 60 healthy controls were enrolled in the study. Disease severity assessment included clinical evaluation with CMT Neuropathy Score version 2 (CMTNSv2). Blood plasma NfL concentrations were measured using the single‐molecule array NfL assay. Results The NfL concentration was significantly higher in the CMT disease patient group than in the controls (p < 0.001). Of the CMT disease patients, those with type CMTX1 had a higher NfL level than those in the two other analysed subgroups (CMT1A and other CMT disease types) (p = 0.0498). The NfL concentration had a significant but weak correlation with the CMTNSv2 (rs = 0.25, p = 0.012). In one CMT disease patient with an extremely elevated NfL level, overlap with chronic inflammatory demyelinating polyneuropathy was suspected. Receiver operating characteristic analysis showed that an NfL concentration of 8.9 pg/ml could be used to discriminate CMT disease patients from controls, with an area under the curve of 0.881. Conclusions Our study confirmed that the plasma NfL concentration is significantly higher in CMT disease patients than in controls. Plasma NfL concentration was found to significantly, albeit weakly, reflect the clinical severity of CMT disease. In the future, NfL may be used, either individually or collaboratively, as a biomarker in the clinical context of suspected CMT disease; however, several issues need to be addressed first.

Neurochemical signs of astrocytic and neuronal injury in acute COVID-19 normalizes during long-term follow-up

“…This raises the question of underestimating the burden of neurology morbidity [29] , although the presence or absence of ongoing neuronal injury may be accurately assessed with NfL [30] . In addition, the wasting of peripheral nerves, a recognized feature in ICU patients, may contribute to increased NfL concentrations, although it cannot explain an increase in GFAp [31] , [32] , [33] .…”

Neurochemical signs of astrocytic and neuronal injury in acute COVID‐19 normalizes during long‐term follow‐up

“…This raises the question of underestimating the burden of neurology morbidity [29] , although the presence or absence of ongoing neuronal injury may be accurately assessed with NfL [30] . In addition, the wasting of peripheral nerves, a recognized feature in ICU patients, may contribute to increased NfL concentrations, although it cannot explain an increase in GFAp [31][32][33] .…”

Role of Blood Neurofilaments in the Prognosis of Amyotrophic Lateral Sclerosis: A Meta-Analysis

“…In summary, although there are relatively few studies on the relationship between blood neurofilament levels and the prognosis of ALS, blood neurofilament levels (NfL/pNfH) may be good predictive biomarkers of ALS patients; that is, higher blood neurofilament levels may be linked to faster DPR and higher risk of death in ALS patients. Although neurofilaments are not specific markers of ALS (e.g., neurofilaments are also promising biomarkers for multiple sclerosis, Alzheimer's disease, and Charcot-Marie-Tooth disease) (46)(47)(48), the predictive effect of neurofilaments on the prognosis of ALS patients suggests to some extent that the pathophysiological mechanism of ALS may be related to changes in the function and concentration of neurofilaments. Besides, neurodegenerative diseases are complex, and biomarkers are just one of the tools to help with diagnosis and treatment.…”