Using the New Biomarkers in Clinical Practice  with Dr. Emily Schorr

Summary

This e-Multiple Sclerosis Review episode features Dr. Emily Shore explaining how emerging biomarkers—blood neurofilament light (NfL) and optical coherence tomography (OCT)—can improve MS care. Through two clinical vignettes, she shows practical interpretation: rising NfL in a 35-year-old (Miss Mar) signals possible uncontrolled disease and prompts reassessment, MRI, adherence support, and treatment discussion; progressive retinal thinning on OCT in a 40-year-old (Miss Edis) reveals subclinical neurodegeneration and supports initiation of high-efficacy therapy. Dr. Shore highlights confounders (age, BMI, kidney function, prior optic neuritis), complementary markers like GFAP, and the need for real-world guidance on testing frequency.

Takeaways

• 😀 Age is a critical factor to account for when interpreting brain atrophy measurements in people with MS.
• 😀 The rate of brain atrophy appears to have greater clinical importance in younger patients with MS.
• 😀 In older patients with MS, observed atrophy may be driven more by normal aging processes than by MS alone.
• 😀 Researchers and clinicians should adjust analyses for important patient factors (like age) to avoid misinterpretation.
• 😀 Two promising biomarkers were highlighted that could meaningfully improve care for people with MS.
• 😀 Biomarkers that track disease-related changes may help personalize monitoring and treatment decisions.
• 😀 Expert perspectives (Dr. Emily Shaw, UC San Diego) were shared to contextualize the biomarker findings.
• 😀 The discussion took place as part of an educational Multiple Sclerosis Review program.
• 😀 Clear communication between experts and clinicians is important to translate biomarker advances into practice.
• 😀 Thoughtful interpretation of imaging and biomarker data is necessary to distinguish MS effects from normal aging.
• 😀 Continued research and validation are implied as needed to confirm how these biomarkers should be used clinically.
• 😀 The program aims to highlight advances that could improve outcomes and care for people living with MS.

Q & A

What is neurofilament light (NFL) and why is it important in multiple sclerosis (MS)?

Neurofilament light (NFL) is a protein found exclusively in neurons that supports their structural integrity. When neurons are damaged, NFL is released into the cerebrospinal fluid and blood. In MS, elevated blood NFL levels indicate neuronal injury, making it a valuable biomarker for monitoring disease activity and treatment response.

What factors other than MS can influence neurofilament light levels in the blood?

Several non-MS factors can elevate NFL levels, including aging, lower body mass index, kidney disease, and other neurological conditions. These must be considered when interpreting NFL results to avoid misattribution to MS activity.

How is NFL currently used in MS clinical practice according to the FDA approval?

NFL is FDA-approved as a biomarker for use in relapsing forms of MS to help assess the risk of near-term relapses. It can indicate active disease, predict relapses and relapse-related disability, and monitor treatment efficacy.

What are the limitations of NFL in evaluating progressive MS?

NFL’s role in progressive MS, independent of relapses, remains unclear. Studies have shown conflicting results, so it is currently more reliable for relapsing MS rather than for tracking progressive disease forms.

How can clinicians interpret a rising NFL level in a patient with MS?

A rising NFL level may indicate increased neuronal damage and uncontrolled MS activity. Clinicians should confirm the result’s validity, consider other potential causes, and possibly adjust treatment or increase monitoring, such as ordering an earlier MRI or discussing stronger therapy options.

What is Optical Coherence Tomography (OCT), and how does it relate to MS care?

OCT is a non-invasive imaging tool that measures retinal layer thickness using light-based technology. It acts like a quantitative ophthalmoscope and provides valuable data correlating with neurodegeneration, brain atrophy, and disease progression in MS.

Which retinal layers are most important in OCT for assessing MS-related changes?

The two most significant layers are the retinal nerve fiber layer (RNFL) and the ganglion cell layer/inner plexiform layer (GCIP). Thinning of these layers correlates with brain atrophy, disease activity, and progression of neurodegeneration in MS.

How can OCT findings influence treatment decisions for MS patients?

If OCT reveals progressive retinal thinning, even in patients who feel symptomatically stable, it may indicate underlying neurodegeneration. This evidence can support initiating or escalating high-efficacy disease-modifying therapy (DMT) to prevent further damage.

How does age affect the interpretation of OCT results in MS patients?

In younger MS patients, retinal thinning seen on OCT is more likely to reflect MS-related neurodegeneration. In older patients, especially over age 55, retinal thinning is often due to normal aging, so results must be interpreted in context.

Are OCT results reliable in patients with optic neuritis or other ophthalmologic comorbidities?

Yes, but clinicians must account for expected changes. After an optic neuritis event, retinal nerve fiber layers initially swell and later atrophy. These patterns are well-documented, allowing clinicians to interpret OCT findings accurately despite comorbidities.

How can combining biomarkers like NFL and GFAP improve MS prognosis and monitoring?

Combining NFL with glial fibrillary acidic protein (GFAP) may offer a more comprehensive view of MS activity. GFAP reflects astrocytic activation, complementing NFL’s measurement of axonal damage, potentially improving prediction of disease course and distinguishing relapsing from progressive MS.

What are the key takeaways from Dr. Emily Shaw’s discussion on biomarkers in MS?

Key points include: NFL and OCT are promising, practical biomarkers for assessing disease activity and progression; results must be interpreted in context with age and comorbidities; combining biomarkers can enhance accuracy; and biomarker data can empower patients to make informed treatment decisions.