Abstract Details

Title Radiographic Determinants of Serum Neurofilament Light Chain Elevation in Multiple Sclerosis

Topic Multiple Sclerosis

Presentation(s) P8 - Poster Session 8 (11:45 AM-12:45 PM)

Poster/Presentation
Number 19-002

Objective To identify features of active lesions associated with elevated sNfL in pwMS.

Background Serum neurofilament light chain (sNfL) is a proposed biomarker in people with multiple sclerosis (pwMS), but elevation with active lesions varies.

Design/Methods We retrospectively identified pwMS ≥20 years meeting 2024 criteria with sNfL measured by Simoa assay. Among 1292 cases reviewed, 299 had ≥1 gadolinium-enhancing lesion on MRI within 90 days of sNfL. All cases were assessed for sNfL elevation (defined by age-adjusted reference data). A stratified cohort (n=83), randomly selected and divided by sNfL status (elevated vs normal), underwent detailed clinical and radiographic review. Wilcoxon rank-sum and Fisher’s exact tests were used.

Results Among 299 pwMS with enhancing lesions, the frequency of sNfL elevation within 3 months was 44% (133/299). In the stratified cohort (35/83 sNfL elevated, 42%), sex (70% female vs. 57%, p=0.25) and timing between MRI and serum (median 4 vs 4.5 days, p=0.99) did not differ between elevated and normal NfL. PwMS with elevated sNfL were younger (median 35 vs 44.5 years, p=0.002). Relapsing-remitting MS was most common (91%). Frequency of enhancing brain (29/34 [83%] vs 36/48 [75%]; p=0.25), and optic nerve (1/35 [3%] vs. 5/48 [10%]; p=0.5) lesions were similar between groups. Enhancing spinal cord lesions were more frequent with elevated sNfL (16/35 [46%] vs 11/48 [23%], p=0.03), as were tumefactive brain lesions (8/35 [23%] vs 2/48 [4%], p=0.04) and diffusion restriction (14/35 [40%] vs 4/48 [8%], p=0.0008). Elevated sNfL was associated with more enhancing brain lesions (median 1 [range 1-33] vs. 1 [1-5], p=0.04) and larger lesion diameter (median 10.4 mm vs 7.1, p=0.04).

Conclusions SNfL elevation occurred in fewer than half of pwMS with enhancing lesions and was more frequent with spinal cord involvement and large diffusion-restricting brain lesions, suggesting regional axonal vulnerability may influence biomarker response.

Authors/Disclosures
Katherine L. Schleiss, MPH PRESENTER	Ms. Schleiss has nothing to disclose.
Hira Chouhdry, MD	Ms. Chouhdry has nothing to disclose.
Pearse Morris, kjsdfkshd	Ms. Morris has nothing to disclose.
Matthew R. Baker, PhD	Dr. Baker has nothing to disclose.
W. O. Tobin, PhD, MBBCh, BAO, FAAN (Mayo Clinic)	Dr. Tobin has received publishing royalties from a publication relating to health care.
Eoin P. Flanagan, MBBCh, FAAN (Mayo Clinic)	The institution of Dr. Flanagan has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Flanagan has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Pharmacy times. The institution of Dr. Flanagan has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for UCB. The institution of Dr. Flanagan has received research support from UCB. The institution of Dr. Flanagan has received research support from Roche. The institution of Dr. Flanagan has received research support from UCB. The institution of Dr. Flanagan has received research support from Merck. The institution of Dr. Flanagan has received research support from Roche. Dr. Flanagan has received publishing royalties from a publication relating to health care. Dr. Flanagan has received publishing royalties from a publication relating to health care. Dr. Flanagan has a non-compensated relationship as a Member of medical Advisory Board with The MOG Project that is relevant to AAN interests or activities. Dr. Flanagan has a non-compensated relationship as a Editorial board member with Journal of The Neurologic Sciences that is relevant to AAN interests or activities. Dr. Flanagan has a non-compensated relationship as a Editorial board member with Neuroimmunology Reports that is relevant to AAN interests or activities. Dr. Flanagan has a non-compensated relationship as a Editorial Board Member with Neurology, Neuroimmunology Neuroinflammation (N2) Journal that is relevant to AAN interests or activities. Dr. Flanagan has a non-compensated relationship as a Editorial Board Member with Neurology that is relevant to AAN interests or activities.
Orhun H. Kantarci, MD	Dr. Kantarci has nothing to disclose.
Mark Keegan, MD, FAAN (Mayo Clinic)	Dr. Keegan has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EMD Serono. Dr. Keegan has received publishing royalties from a publication relating to health care. Dr. Keegan has received publishing royalties from a publication relating to health care.
M. M. Paz Soldan, MD, PhD (Mayo Clinic)	Dr. Paz Soldan has received personal compensation in the range of $500-$4,999 for serving as a Consultant for TG Therapeutics. The institution of Dr. Paz Soldan has received research support from National Institutes of Health. The institution of Dr. Paz Soldan has received research support from National Multiple Sclerosis Society. The institution of Dr. Paz Soldan has received research support from Western Institute for Biomedical Research. The institution of Dr. Paz Soldan has received research support from Biogen. The institution of Dr. Paz Soldan has received research support from Novartis. The institution of Dr. Paz Soldan has received research support from Clene Nanomedicine.
Sean J. Pittock, MD, FAAN (Mayo Clinic Dept of Neurology)	Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Arialys. The institution of Dr. Pittock has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. The institution of Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB. The institution of Dr. Pittock has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche/Genentech. The institution of Dr. Pittock has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Alexion/AstraZeneka. The institution of Dr. Pittock has received research support from NIH. Dr. Pittock has received intellectual property interests from a discovery or technology relating to health care. Dr. Pittock has received intellectual property interests from a discovery or technology relating to health care. Dr. Pittock has received publishing royalties from a publication relating to health care.
Samantha Banks, MD	Dr. Banks has nothing to disclose.

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