Beneath the Surface: How a Simple Blood Test Is Transforming MS Treatment Monitoring

Multiple sclerosis (MS) is a disease of many disguises—often progressing silently beneath the surface even when patients appear clinically stable. What if we had a simple blood test that could alert us to this hidden activity? Enter neurofilament light chain (NfL), a promising biomarker that may soon redefine how we monitor and treat MS.

A recent expert-led perspective published in Frontiers in Neurology by Centonze and colleagues (2025) charts a practical roadmap for integrating blood NfL (bNfL) testing into MS clinical care. By identifying key patient profiles that would benefit most, this initiative aims to improve disease surveillance and guide timely treatment decisions—especially in settings where access to MRI is limited.

What Is bNfL and Why Does It Matter?
Neurofilament light chain is a structural protein in neurons, released into the cerebrospinal fluid and blood when axons are damaged. With sensitive technologies like SiMoA (single-molecule array), bNfL can now be detected in the bloodstream at minute levels. This means a simple blood draw could give clinicians insights into the invisible damage occurring in a patient’s nervous system.

High bNfL levels are associated with MS relapses, new or enlarging MRI lesions, disability progression, and even future brain atrophy. Perhaps most excitingly, elevated levels can precede clinical relapses by months, opening the door to proactive intervention.

Beyond MRI: A Complementary Lens for MS Management
MRI remains a cornerstone of MS diagnosis and monitoring—but it's not always accessible, and its ability to detect subtle or spinal cord damage is limited. Here, bNfL offers several advantages:

Wider Detection Window: Gadolinium-enhancing lesions on MRI are transient, whereas bNfL levels stay elevated for ~3 months after axonal injury.

Cost-Effectiveness: Regular bNfL testing may reduce the need for frequent MRI, easing the financial and logistical burden on healthcare systems.

Real-Time Monitoring: Unlike MRI, which may lag behind current disease activity, bNfL reflects neurodegeneration as it happens.

Who Should Get Tested? Patient Profiles to Prioritize
Recognizing that widespread testing is not yet feasible, the authors emphasize a targeted approach, focusing on high-yield scenarios:

1. Clinically Stable, But Symptomatic
Patients who seem stable yet present subtle red flags—fatigue, mood changes, or early cognitive symptoms—could be harboring subclinical disease. Regular bNfL monitoring (every 4–5 months) can detect hidden activity and guide more aggressive management if needed.

2. Off-Treatment or Post-Induction Therapy
Those in a drug-free interval or after immune-reconstitution therapies (like cladribine or alemtuzumab) benefit from biannual bNfL checks. Rising levels could signal the need to restart or modify treatment.

3. Pregnant or Planning Pregnancy
MS relapse risk drops during pregnancy but spikes postpartum. While data on bNfL in pregnancy are limited, preliminary studies show its potential for detecting relapse early—especially in untreated women.

4. JCV-Positive Patients on Natalizumab
Given their risk for PML (a rare but serious brain infection), these patients require close monitoring. bNfL may serve as an early warning tool, especially when MRI is inconclusive.

When to Re-Test?
Experts suggest establishing a baseline bNfL measurement—ideally when the patient is stable—and repeating it every 4–6 months depending on the clinical context. Longitudinal tracking is key: rather than focusing on isolated readings, trends over time offer more clinically relevant insight.

Limitations and the Path Forward
While promising, bNfL isn’t a magic bullet. It’s not disease-specific and can be elevated by other neurological or systemic conditions. Age, comorbidities, BMI, and even recent physical activity can influence levels. However, using Z-scores and personalized baselines can help clinicians interpret results more accurately.

Moreover, bNfL may not fully capture the smoldering, non-inflammatory progression seen in progressive MS. In such cases, complementary biomarkers like glial fibrillary acidic protein (GFAP) might offer added value.

Disclaimer: This blog post is based on the provided research article and is intended for informational purposes only. It is not intended to provide medical advice. Please consult with a healthcare professional for any health concerns.

References:
Centonze, D., Di Sapio, A., Brescia Morra, V., Colombo, E., Inglese, M., Paolicelli, D., ... & Furlan, R. (2025). Steps toward the implementation of neurofilaments in multiple sclerosis: patient profiles to be prioritized in clinical practice. Frontiers in Neurology, 16, 1571605.