Neurofilaments in progressive multiple sclerosis: a systematic review

Abstract

Background Neurofilament proteins have been extensively studied in relapsing-remitting multiple sclerosis, where they are promising biomarkers of disease activity and treatment response. Their role in progressive multiple sclerosis, where there is a particularly urgent need for improved biomarkers, is less clear. The objectives of this systematic review are to summarise the literature on neurofilament light and heavy in progressive multiple sclerosis, addressing key questions. Methods A systematic search of PubMed, Embase, Web of Science and Scopus identified 355 potential sources. 76 relevant sources were qualitatively reviewed using QUADAS-2 criteria, and 17 were identified as at low risk of bias. We summarise the findings from all relevant sources, and separately from the 17 high-quality studies. Results Differences in neurofilament light between relapsing-remitting and progressive multiple sclerosis appear to be explained by differences in covariates. Neurofilament light is consistently associated with current inflammatory activity and future brain atrophy in progressive multiple sclerosis, and is consistently shown to be a marker of treatment response with immunosuppressive disease-modifying therapies. Associations with current or future disability are inconsistent, and there is no evidence of NFL being a responsive marker of purportedly neuroprotective treatments. Evidence on neurofilament heavy is more limited and inconsistent. Conclusions Neurofilament light has shown consistent utility as a biomarker of neuroinflammation, future brain atrophy and immunosuppressive treatment response at a group level. Neither neurofilament light or heavy has shown a consistent treatment response to neuroprotective disease-modifying therapies, which will require further data from successful randomised controlled trials.

Neurofilamentai kraujo serume: neuronų pažeidimo biožymuo išsėtinės sklerozės paūmėjimo metu

“…Ac cord ing to the lat est metaanal y sis, not all NFL-L and NFL-H stud ies have shown a con sis tent re duc tion of NFL lev els in pa tients treated with DMTs. There fore, in or der to use NFL con cen tra tion in blood se rum as a treat ment mon i tor ing tool, ad di tional large sam ple size, ran dom ized con trolled clin i cal stud ies are nec es sary [16]. Anal y sis of data of 271 pa tients with clin i cally iso lated syn drome has re vealed a high prob a bil ity (97% sen si tiv ity) of de vel op ing mul ti ple scle ro sis if high lev els of NFL and pos i tive oligoclonal bands are found in the cerebro spinal fluid [17].…”

CSF1R-Related Leukoencephalopathy Caused by CSF1R p.Arg777Trp and CSF1R p.Arg782Cys Mutations: A Report of Four Cases in Sweden

“…This is consistent with the NFL level in case 1. However, Patients 3 and 4 indicate that CSF-NFL may be only moderately elevated, as commonly seen in MS (relapsing and progressive) and atypical parkinsonism (33)(34)(35).…”

Neurofilament light chain in demyelinating conditions of the central nervous system: a promising biomarker

“…Finally, treatments with DMTs including natalizumab, rituximab, fingolimod, ocrelizumab, and mitoxantrone seem to affect plasma NfL levels. Unestablished treatments, first-line DMTs, or neuroprotective treatments seem less effective in influencing NfL values [66] .…”