 |
Publisher: Peytchinski Publishing Ltd.
ISSN: 1312-773X (Online)
Issue: 2024, vol. 30, issue2
Subject Area: Medicine
-
DOI: 10.5272/jimab.2024302.5527
Published online: 20 May 2024
Review article
J of IMAB. 2024 Apr-Jun;30(2):5527-5532
NEUROFILAMENTS AS A POTENTIAL BIOMARKER IN PATIENTS WITH MULTIPLE SCLEROSIS: A REVIEW OF LITERATURE
Magdalina Yanakieva
, Maya Danovska, Emilia Ovcharova, Diana Marinova,
Department of Neurology, Faculty of Medicine, Medical University - Pleven, Bulgaria.
ABSTRACT:
Background: Multiple sclerosis (MS) is a chronic inflammatory neurodegenerative disease of the central nervous system (CNS) characterized by demyelination, axonal damage and loss of neurons. Its growing incidence has determined the need for more intensive research towards effective models for managing disease progression and evaluation of treatment response. Finding clinically relevant biomarkers has been a significant challenge.
Purpose: This review aims to summarize the findings from current relevant literature sources on neurofilaments as a potential biomarker of diagnostic and prognostic value in patients with MS.
Results: Recently, neurofilaments have been identified as the most promising and informative biomarkers of axonal damage and loss. Neurofilament concentration demonstrates a strong association with the disease course, activity and progression, disability accumulation and response to disease-modifying treatment. A significant correlation with future relapse rates, symptom worsening and risk of conversion from clinically isolated syndrome (CIS) to definite MS has also been established. Several MS therapies have demonstrated a substantial reduction in neurofilament levels upon treatment initiation.
Conclusion: The results available from real-world studies and clinical trials regarding neurofilaments as a reliable predictor and indicator of MS disease course are encouraging. They have consistently proven to be of utility if integrated into the diagnostic and therapeutic algorithm of MS patients. This review encompasses undeniable data confirming the considerable potential of neurofilaments for becoming the first globally verified biomarker for MS. The accessibility, safety, low cost and possibility for serial evaluation make the neurofilaments the perfect component to be implemented in routine clinical tests for MS.
Keywords: multiple sclerosis, biomarkers, neurofilaments, disease progression, disability, disease-modifying treatment,
- Download FULL TEXT /PDF 502 KB/
Please cite this article as: Yanakieva M, Danovska M, Ovcharova E, Marinova D. Neurofilaments as a potential biomarker in patients with multiple sclerosis: a review of literature. J of IMAB. 2024 Apr-Jun;30(2):5527-5532. [Crossref - 10.5272/jimab.2024302.5527]
Correspondence to: Magdalina Yanakieva, Department of Neurology, Faculty of Medicine, Medical University – Pleven; 1, Kliment Ohridski Str., 5800 Pleven, Bulgaria; E-mail: m.yanakieva94@gmail.com
REFERENCES:
1. Milanov I, Traykov L, Tarnev I, Bojinova V, Maslarov D, Kaprelyan A, et al. National Consensus on Diagnosis and Treatment of Multiple Sclerosis. Edited by I. Milanov. Bulgarian Society of Neurology. 15 March 2021. 79p. [Internet]
2. Reich DS, Lucchinetti CF, Calabresi PA. Multiple sclerosis. N Engl J Med. 2018 Jan 11;378(2):169-180 [PubMed]
3. Igra MS, Paling D, Wattjes MP, Connolly DJA, Hoggard N. Multiple sclerosis update: use of MRI for early diagnosis, disease monitoring and assessment of treatment related complications. Br J Radiol. 2017 Jun;90(1074):20160721. [ PubMed ]
4. Gnanapavan S, Giovannoni G. Developing Biomarkers for MS. Curr Top Behav Neurosci. 2015;26:179-94. [PubMed]
5. Lassmann H, Brück W, Lucchinetti C. Heterogeneity of multiple sclerosis pathogenesis: implications for diagnosis and therapy. Trends Mol Med. 2001 Mar;7(3):115-21. [PubMed]
6. Dobson R, Giovannoni G. Multiple sclerosis - a review. Eur J Neurol. 2019 Jan;26(1):27-40. [PubMed]
7. Gasperini C, Prosperini L, Tintoré M, Sormani MP, Filippi M, Rio J, et al. Unraveling treatment response in multiple sclerosis: A clinical and MRI challenge. Neurology. 2019 Jan 22;92(4):180-192. [PubMed]
8. Barkhof F. The clinico-radiological paradox in multiple sclerosis revisited. Curr Opin Neurol. 2002 Jun;15(3):239-45. [ PubMed]
9. Gentil BJ, Tibshirani M, Durham HD. Neurofilament dynamics and involvement in neurological disorders. Cell Tissue Res. 2015 Jun;360(3):609–20. [PubMed]
10. Teunissen CE, Khalil M. Neurofilaments as biomarkers in multiple sclerosis. Mult Scler. 2012 May;18(5):552-6. [PubMed]
11. Khalil M, Pirpamer L, Hofer E, Voortman MM, Barro C, Leppert D, et al. Serum neurofilament light levels in normal aging and their association with morphologic brain changes. Nat Commun. 2020 Feb 10;11(1):812. [PubMed]
12. Jordanova A, De Jonghe P, Boerkoel CF, Takashima H, De Vriendt E, Ceuterick C, et al. Mutations in the neurofilament light chain gene (NEFL) cause early onset severe Charcot-Marie-Tooth disease. Brain. 2003 Mar;126(Pt 3):590-7. [PubMed]
13. Figlewicz DA, Krizus A, Martinoli MG, Meininger V, Dib M, Rouleau GA, et al. Variants of the heavy neurofilament subunit are associated with the development of amyotrophic lateral sclerosis. Hum Mol Genet. 1994 Oct;3(10):1757–61. [PubMed]
14. Qu Y, Tan CC, Shen XN, Li HQ, Cui M, Tan L, et al. Association of Plasma Neurofilament Light With Small Vessel Disease Burden in Nondemented Elderly: A Longitudinal Study. Stroke. 2021 Mar;52(3):896-904. [PubMed]
15. Zivadinov R, Bergsland N, Dwyer MG. Atrophied brain lesion volume, a magnetic resonance imaging biomarker for monitoring neurodegenerative changes in multiple sclerosis. Quant Imaging Med Surg. 2018 Nov;8(10):979-983. [PubMed]
16. Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983 Nov;33(11):1444-52. [PubMed]
17. Li DK, Held U, Petkau J, Daumer M, Barkhof F, Fazekas F et al. Centre for MS Research. MRI T2 lesion burden in multiple sclerosis: a plateauing relationship with clinical disability. Neurology. 2006 May 9;66(9):1384-9. [PubMed]
18. Gajofatto A, Benedetti MD. Treatment strategies for multiple sclerosis: When to start, when to change, when to stop? World J Clin Cases. 2015 Jul 16;3(7):545-55. [PubMed]
19. Yang J, Hamade M, Wu Q, Wang Q, Axtell R, Giri S, Mao-Draayer Y. Current and Future Biomarkers in Multiple Sclerosis. Int J Mol Sci. 2022 May 24;23(11):5877. [PubMed]
20. Disanto G, Barro C, Benkert P, Naegelin Y, Schädelin S, Giardiello A, et al. Serum Neurofilament light: A biomarker of neuronal damage in multiple sclerosis. Ann Neurol. 2017 Jun;81(6):857-870. [PubMed]
21. Axelsson M, Malmeström C, Gunnarsson M, Zetterberg H, Sundström P, Lycke J, et al. Immunosuppressive therapy reduces axonal damage in progressive multiple sclerosis. Mult Scler. 2014 Jan;20(1):43-50. [PubMed]
22. Brownlee WJ, Hardy TA, Fazekas F, Miller DH. Diagnosis of multiple sclerosis: progress and challenges. Lancet. 2017 Apr 1;389(10076):1336-1346. [PubMed]
23. Bittner S, Steffen F, Uphaus T, Muthuraman M, Fleischer V, Salmen A, et al. Clinical implications of serum neurofilament in newly diagnosed MS patients: A longitudinal multicentre cohort study. EBioMedicine. 2020 Jun;56:102807. [PubMed]
24. Jakimovski D, Kuhle J, Ramanathan M, Barro C, Tomic D, Hagemeier J, et al. Serum neurofilament light chain levels associations with gray matter pathology: a 5-year longitudinal study. Ann Clin Transl Neurol. 2019 Sep;6(9):1757-1770. [PubMed]
25. Bergman J, Dring A, Zetterberg H, Blennow K, Norgren N, Gilthorpe J, et al. Neurofilament light in CSF and serum is a sensitive marker for axonal white matter injury in MS. Neurol Neuroimmunol Neuroinflamm. 2016 Aug 2;3(5):e271. [PubMed]
26. Varhaug KN, Barro C, Bjørnevik K, Myhr KM, Torkildsen Ø, Wergeland S, et al. Neurofilament light chain predicts disease activity in relapsing-remitting MS. Neurol Neuroimmunol Neuroinflamm. 2017 Nov 28;5(1):e422. [PubMed]
27. Rovaris M, Confavreux C, Furlan R, Kappos L, Comi G, Filippi M. Secondary progressive multiple sclerosis: current knowledge and future challenges. Lancet Neurol. 2006 Apr;5(4):343-54. [PubMed]
28. Ferraro D, Guicciardi C, De Biasi S, Pinti M, Bedin R, Camera V, et al. Plasma neurofilaments correlate with disability in progressive multiple sclerosis patients. Acta Neurol Scand. 2020 Jan;141(1):16-21. [PubMed]
29. Leppert D, Kropshofer H, Häring DA, Dahlke F, Patil A, Meinert R, et al. Blood Neurofilament Light in Progressive Multiple Sclerosis: Post Hoc Analysis of 2 Randomized Controlled Trials. Neurology. 2022 May 24;98(21):e2120-e2131. [PubMed]
30. Hauser SL, Cree BAC. Treatment of Multiple Sclerosis: A Review. Am J Med. 2020 Dec;133(12):1380-1390.e2. [PubMed]
31. Mayssam EN, Eid C, Khoury SJ, Hannoun S. "No evidence of disease activity": Is it an aspirational therapeutic goal in multiple sclerosis? Mult Scler Relat Disord. 2020 May;40:101935. [PubMed]
32. Cree BAC, Hollenbach JA, Bove R, Kirkish G, Sacco S, Caverzasi E, et al. Silent progression in disease activity-free relapsing multiple sclerosis. Ann Neurol. 2019 May;85(5):653-666. [PubMed]
33. Khoy K, Mariotte D, Defer G, Petit G, Toutirais O, Le Mauff B. Natalizumab in Multiple Sclerosis Treatment: From Biological Effects to Immune Monitoring. Front Immunol. 2020 Sep 24;11:549842. [PubMed]
34. Dalla Costa G, Martinelli V, Moiola L, Sangalli F, Colombo B, Finardi A, et al. Serum neurofilaments increase at progressive multifocal leukoencephalopathy onset in natalizumab-treated multiple sclerosis patients. Ann Neurol. 2019 Apr;85(4):606-610. [PubMed]
35. Liu N, Sun M, Zhang W, Sun J, Gong P, Wang H, et al. Prognostic value of neurofilament light chain in natalizumab therapy for different phases of multiple sclerosis: A systematic review and meta-analysis. J Clin Neurosci. 2022 Jul;101:198-203. [PubMed]
36. Scott LJ. Siponimod: A Review in Secondary Progressive Multiple Sclerosis. CNS Drugs. 2020 Nov;34(11):1191-1200. [PubMed]
37. Alvarez E, Kuhle J, Kappos L, Ziemssen T, Arnold D, Cross A, et al. Long-term Effect of Ofatumumab Treatment on Serum Neurofilament Light Chain Levels and NEDA-3 Status in Patients With RMS: Results From ASCLEPIOS I/II and ALITHIOS. Neurology. 2023 Apr 25;100(17 Suppl 2):P6-3.013. [Crossref]
38. Gaetani L, Blennow K, Calabresi P, Di Filippo M, Parnetti L, Zetterberg H. Neurofilament light chain as a biomarker in neurological disorders. J Neurol Neurosurg Psychiatry. 2019 Aug;90(8):870-881. [PubMed]
Received: 22 January 2024
Published online: 20 May 2024