Neurofilament Light Chain in the Clinic: Applications and Limitations in the Management of Multiple Sclerosis
Micah Hamilton1, Grace Inserra1, Cate Ledoux1, Nicholas Streicher1
1Georgetown University
Objective:
To determine whether commercially obtained serum neurofilament light chain (NfL) levels were associated with MRI-based markers of multiple sclerosis (MS) progression and relapse.
Background:
Neurofilament light chain (NfL), a neuronal cytoskeletal protein, is a marker of active or recent axonal damage in various neurodegenerative disorders, including MS. Prior work has associated higher serum NfL levels with faster progression of MS as measured by the Expanded Disability Severity Scale (EDSS), highlighting its prognostic value.
Design/Methods:
We conducted an IT-based data extraction to review all serum NfL test results (Dec 2022-Jan 2025) commercially ordered by MS providers in our clinic (n=447). We then reviewed neuroimaging results from associated MRI procedures to determine whether a relapse had occurred close to the time of serum NfL testing. For our preliminary analysis, we reviewed available neuroimaging for all NfL results considered elevated according to commercial guidelines (n=28) and a random subsample of non-elevated results (n=30). Patients were then categorized as relapsing if new enhancing lesions were identified in radiology reports.
Results:
The mean NfL result for the relapsing group was greater than for non-relapsing, but not significantly (Two Sample t-test t = 1.7542, df = 56, p = .085). Similarly, a greater proportion of patients with elevated NfL results were relapsing, but the difference was not significant, X2 (1, N = 60) = 2.8, p = 0.092.
Conclusions:
Our borderline-significant results indicate that further investigation into the relationship between NfL and MS disease progression is needed. Thus far, NfL does not demonstrate the specificity required to replace neuroimaging in identifying relapses. However, it may be useful in identifying patients with subclinical progression that is undetectable on MRI. With further refinement of the interpretation of NfL, clinicians could use this test to identify patients who need changes in medication to slow disease progression.
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