Evaluating neurofilaments as a reliable biomarker for Multiple Sclerosis

Background and Purpose: Multiple Sclerosis(MS) is an autoimmune disease in the central nerves system(CNS) lead to axonal damage and neurodegeneration even in the early phase. Due to the increase of incidence in worldwide and new therapeutic methods and medicines provided, the existence of a reliable biomarker for saying something about the stage of the disease, the prognosis and the response to treatment is necessary. Our aim is to evaluate the neurofilaments when the neuron degeneration released as a biomarker for MS. Method: In this systematic review, the keywords of Multiple Sclerosis biomarkers, neurofilaments and Multiple Sclerosis, neurodegeneration biomarkers in the title and abstract of articles in the international databases, PUBMED and Science Direct were searched, that through existing research 60 relate articles were obtained, with study of the articles abstract, 21 articles choice for comprehensive review. Results: Neurofilaments(NFs) belong to intermediate filament family of proteins where in neurons as cytoskeletal component and contain three subunits: neurofilament light chain (NF-L), neurofilament medium (NF-M) and neurofilament heavy (NF-H). Axonal damage by inflammation and autoimmunity mechanisms cause NFs released into the cerebrospinal fluid(CSF) and also those reach the blood through CNS drainages. Both NF-L and NF-H studied as potential biomarkers in MS and both of them show the positive association with Expanded Disability Status Scale (EDSS) in patients with Relapse-Remission (RRMS) but investigation suggests that NF-L discriminates better than NF-H between MS and controls. Studies suggested that the CSF NF-L levels higher in RRMS, Primary Progressive MS(PPMS) and Secondary Progressive MS(SPMS) compared with healthy controls. Also, some analysis shows that CSF NF-L levels in RRMS higher than progressive MS but no significant difference was detected between PPMS and SPMS. Follow-up MS patients by CSF NF-L level and compared them to themselves after the treatment was started or untreated groups show the significant decrease of CSF NF-L level in treated groups also every type of treatment change CSF NF-L levels differently that can utilize this difference as the biomarker for evaluating response to treatment in MS patients. Use of NF-L level as a biomarker for prognosis and the response to treatment faces several problems such as CSF sampling is hard and painful for patients, although NF-L reach serum but serum levels approximately 42-fold lower than CSF that needs to sufficiently sensitive methods of detection also NF-L level in serum and CSF depend on age and personal differences in the degree of protein leakage through the Blood Brain Barrier(BBB). Conclusion: Serum and CSF NF-L levels depend on several factor that one of them is axonal damage by reason of MS also detecting NF-L in serum need sufficiently sensitive techniques, if these problems will solve, CSF and serum NF-L levels can be used as a reliable biomarker beside another biomarker for evaluating response to treatment, prognosis and maybe diagnosis of MS in near future.

کلیدواژه ها:

Neurofilament and Multiple Sclerosis ، Biomarker ، Multiple Sclerosis Biomarker ، Multiple Sclerosis