Multiple sclerosis monitoring profile
Blood biomarkers (BBMs) are a new frontier in neurology, impacting the way physicians diagnose, manage and monitor neurodegenerative diseases such as Alzheimer’s and ALS. The promise of BBMs, particularly neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP), to change and improve multiple sclerosis (MS) patient management is now being realized.
NfL and GFAP are two BBMs that are not specific to any condition, but when employed within a particular clinical context can be helpful for evaluating, diagnosing or managing a number of neurodegenerative diseases. NfL is a structural protein found only in the axons of neurons.1 As MS is a disease of demyelination and subsequent neuronal damage, NfL has been studied extensively in MS patients. NfL levels are increased in early relapsing MS and have been shown to correlate with markers of disease severity.2 Treatment with disease-modifying therapy has been reported to be associated with lower NfL levels compared to untreated individuals.3
Though NfL is now well established as an important marker for evaluating acute disease activity and relapses,2-4 it is not a helpful marker for monitoring disease progression independent of relapse activity (PIRA).5 Instead, GFAP has been investigated for this purpose and has been demonstrated to be a predictor of PIRA in both relapsing-remitting and progressive forms of MS.6,7 Additionally, serial GFAP measurements can be a marker of disease severity.7,8
Together, NfL and GFAP are new ways of helping physicians evaluate and monitor MS patients with simple blood draws that not only complement MRI but may also lead to a reduction in the frequency of MRI. In December of 2023, the Consortium of Multiple Sclerosis Centers (CMSC) published consensus panel recommendations for the use of NfL in MS patients. Specifically, the panel provided recommendations for testing NfL in patients prior to therapy initiation, and every 3 to 6 months post initiation to monitor for therapeutic efficacy.9 Although formal recommendations for GFAP have not yet been established at the time of this writing, monitoring for PIRA using GFAP at the same time intervals as recommended for NfL for therapeutic monitoring is clinically justifiable and does not impose a greater burden on patients.
MS monitoring profile
As both NfL and GFAP serve important, yet different, roles in monitoring MS patient disease progression and therapeutic efficacy, Labcorp combined these two important markers in a panel to enable easier ordering and side-by-side interpretation of these synergistic markers. Both NfL and GFAP employ aged-based reference ranges to determine whether the level being measured in any patient is abnormally high. Additionally, z-scores are used to help understand the degree to which any abnormal value has surpassed the cutoff. These markers have been studied in relapsing-remitting and progressive forms of MS and can provide quantitative assessments to track and monitor MS patients on B-cell depleting treatments in a less burdensome and more frequent way relative to imaging.
Test Name | Test Number |
---|---|
Multiple Sclerosis Monitoring Profile | 484495 |
References
References
1. Yuan A, Rao MV, Veeranna, Nixon RA. Neurofilaments and neurofilament proteins in health and disease. Cold Spring Harb Perspect Biol. 2017;9(4):a018309. doi:10.1101/cshperspect.a018309
2. Thebault S, Booth RA, Rush CA, MacLean H, Freedman MS. Serum neurofilament light chain measurement in MS: hurdles to clinical translation. Front Neurosci. 2021;15:654942. doi:10.3389/fnins.2021.654942
3. Calabresi PA, Arnold DL, Sangurdekar D, et.al. Temporal profile of serum neurofilament light in multiple sclerosis: Implications for patient monitoring. Mult Scler. 2021;27(10):1497-1505. doi:10.1177/1352458520972573
4. Khalil M, Teunissen CE, Otto M, et al. Neurofilaments as biomarkers in neurological disorders. Nat Rev Neurol. 2018;14(10):577-589. doi:10.1038/s41582-018-0058-z
5. Gafson AR, Jiang X, Shen C, et al. Serum neurofilament light and multiple sclerosis progression independent of acute inflammation. JAMA Netw Open. 2022;5(2):e2147588. doi:10.1001/jamanetworkopen.2021.47588
6. Meier S, Willemse EA, Schaedelin S, et al. Serum glial fibrillary acidic protein compared with neurofilament light chain as a biomarker for disease progression in multiple sclerosis. JAMA Neurol. 2023;80(3):287-297. doi:10.1001/jamaneurol.2022.5250
7. Abdelhak A, Hottenrott T, Morenas-Rodríguez E, et al. Glial activation markers in CSF and serum from patients with primary progressive multiple sclerosis: potential of serum GFAP as disease severity marker? Front Neurol. 2019;10:280. doi:10.3389/fneur.2019.00280
8. Abdelhak A, Huss A, Kassubek J, Tumani H, Otto M. Serum GFAP as a biomarker for disease severity in multiple sclerosis. Sci Rep. 2018;8(1):14798. doi:10.1038/s41598-018-33158-8
9. Consortium of Multiple Sclerosis Centers (CMSC) best practices for the use of serum neurofilament (sNfL) in MS management. Consortium of Multiple Sclerosis Centers. Updated January 2024. https://www.mscare.org/page/NFL