Abstract Details

Title Serum Neurofilament Light Chain Levels Differentiate Spinal Cord Infarction from Inflammatory Myelitis

Topic Multiple Sclerosis

Presentation(s) S10 - Multiple Sclerosis: Biomarkers and Outcome Measures (4:06 PM-4:18 PM)

Poster/Presentation
Number 004

Objective

To investigate whether serum neurofilament light chain (NfL) levels differentiate spinal cord infarction (SCI) from inflammatory myelitis.

Background Spontaneous SCI is a cause of acute myelopathy for which no specific biomarker is currently available. Aquaporin-4 (AQP4)-IgG –associated myelitis is a particularly severe alternative acute myelopathy etiology with features overlapping SCI, and is reliably diagnosed with AQP4-IgG seropositivity. We hypothesized that acute serum NfL levels (a biomarker of neuronal damage in the central nervous system) would be higher in SCI than AQP4-IgG-associated myelitis, and therefore a potentially useful diagnostic biomarker to differentiate SCI from inflammatory myelitis.

Design/Methods

We retrospectively identified Mayo Clinic patients with: 1) SCI; or 2) treatment-naïve AQP4-IgG-associated myelitis at clinical presentation; and 3) stored serum sample obtained ≤2 months from onset. Serum NfL levels were assessed at the Verona University Neuropathology laboratory (SIMOA Quanterix) in a blinded fashion. Representative sagittal cross-sectional spinal cord lesion areas were manually drawn.

Results Twenty-eight patients were included: SCI, 17; AQP4-IgG-associated myelitis, 11. Median age (range) at serum sampling (57 [42-86] vs 59 [14-73] years; p=0.6), frequency of female gender (8/17 [47%] vs 9/11 [82%]; p=0.12), and longitudinally extensive lesions (>3 contiguous vertebral-body segments) on MRI (10/16 [63%] and 9/11 [82%]; p=0.4) were similar in the two groups. Serum NfL levels in patients with SCI (median 224.83 [range, 14.26-2793.41] pg/mL) far exceeded those with AQP4-IgG-associated myelitis (median 56.16 [range, 8.17-687.22] pg/mL); p=0.015. The ratio of NfL levels to cross-sectional lesion area showed high predictive accuracy for SCI with values greater than 0.54 yielding 100% specificity and 94% sensitivity for SCI (AUC=0.99).

Conclusions

The ratio of serum NfL/lesion area reliably distinguished SCI from AQP4-IgG myelitis. Serum NfL/lesion area may be a useful biomarker to differentiate SCI from alternative acute myelopathy etiologies, such as inflammatory myelitis.

Authors/Disclosures
Nicholas L. Zalewski, MD (Mayo Clinic) PRESENTER	Dr. Zalewski has nothing to disclose.
Elia Sechi, MD (University of Sassari)	Dr. Sechi has nothing to disclose.
Andrew McKeon, MD (Mayo Clinic)	The institution of Dr. McKeon has received research support from National Institutes of Health. Dr. McKeon has received intellectual property interests from a discovery or technology relating to health care. Dr. McKeon has received intellectual property interests from a discovery or technology relating to health care. Dr. McKeon has received publishing royalties from a publication relating to health care.
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 UCB. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Arialys Therapeutics. 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. 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 Arialys. 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. The institution of Dr. Pittock has received research support from Alexion/AstraZeneka. The institution of Dr. Pittock has received research support from F. Hoffman/LaRoche/Genentech. 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.
	No disclosure on file
	No disclosure on file
Eoin P. Flanagan, MBBCh, FAAN (Mayo Clinic)	The institution of Dr. Flanagan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Flanagan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Flanagan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon Therapeutics. 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 Viela Bio. The institution of Dr. Flanagan has received research support from UCB. 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 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.
Alejandro A. Rabinstein, MD, FAAN (Mayo Clinic)	Dr. Rabinstein has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Boston Scientific. Dr. Rabinstein has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Shionogi . Dr. Rabinstein has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Chiesi. Dr. Rabinstein has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Ceribell. Dr. Rabinstein has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neurocritical care/NCS-Springer. Dr. Rabinstein has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Wolters/UptoDate. Dr. Rabinstein has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for EBSCO/DynaMed. Dr. Rabinstein has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for AHA. Dr. Rabinstein has received publishing royalties from a publication relating to health care. Dr. Rabinstein has received publishing royalties from a publication relating to health care. Dr. Rabinstein has received publishing royalties from a publication relating to health care. Dr. Rabinstein has received publishing royalties from a publication relating to health care.
Sara Mariotto, MD, PhD (Neurology Unit, University of Verona)	Dr. Mariotto has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Biogen, Sanofi, Alexion, Roche, TSF, Dynamics, UCB, Novartis, Amgen, AAN. The institution of Dr. Mariotto has received research support from Ministero della Salute Italiano. The institution of Dr. Mariotto has received research support from TSF. The institution of Dr. Mariotto has received research support from GJF. The institution of Dr. Mariotto has received research support from Lundbeck.

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