The Role of Neurofilaments in Diagnosis and Monitoring of Amyotrophic Lateral Sclerosis

Background: Amyotrophic lateral sclerosis (ALS), the most common type of motor neurone disease (MND), is a devastating diagnosis that often leads to mortality within 2-5 years of symptom onset. Respiratory failure and aspiration pneumonia both associated with respiratory muscle weakness are the most common causes of death. Difficult to diagnose and devastating in its prognosis, much research has aimed to identify a reliable biomarker to diagnose ALS, prognosticate and improve enrolment into clinical trials to further research efforts. Over the last few decades, neurofilaments (NFs) have emerged as promising biomarkers, especially neurofilament light chain (NFL) and phosphorylated neurofilament heavy chain (pNFH). This review aims to summarise the current evidence for use of NFs as biomarkers in ALS. Current Evidence: Higher levels of NFL and pNFH are measured in CSF than in serum, and levels in CSF and serum are correlated. High CSF NFL, serum NFL and CSF pNFH levels could differentiate patients with ALS from healthy controls, other neurological disease, neurodegenerative controls (without MND), other MND subtypes and ALS disease mimics; however, studies reported a high degree of heterogeneity irrespective of which media or NFs have been used. The number of studies examining NFs to predict respiratory failure in patients with ALS is low. Conclusions and Future Directions: Despite numerous studies consistently reporting higher NF levels in ALS compared to various controls, their clinical value is limited due to high heterogeneity of the results and inconsistencies in proving its prognostic value. Further understanding the relationship between NF levels and respiratory failure is paramount to improve the quality of life of patients with ALS and increase survival.