Abstract Details

Title Adjusting neurofilament light levels using an MRI-based estimate of total axonal bulk improves its prediction of MS progression

Topic Multiple Sclerosis

Presentation(s) P5 - Poster Session 5 (5:30 PM-6:30 PM)

Poster/Presentation
Number 15-004

Objective To improve the utility of NfL as a biomarker of MS disease progression using quantitative brain MRI data to adjust for a patient's total axonal bulk.

Background Neurofilament Light Chain (NfL) is a scaffolding protein of the neural cytoskeleton with roles in axonal growth. Increased NfL levels in the cerebrospinal fluid (CSF) have been implicated as a biomarker of neurodegeneration in Multiple Sclerosis (MS) and other neurological diseases. Although increased NfL CSF levels have been associated with progression of neurological disability, its predictive power is low. Because NfL is measured in CSF of HVs, often with values overlapping with neurological patients, we hypothesized that there are two pools of CSF NfL: 1. Physiological pool, associated with processes such as axonal maintenance and 2. Pathological pool, associated with axonal transections. The extension of this hypothesis is that the physiological pool of NfL will depend on the proportion of the axonal bulk to CSF volume.

Design/Methods We estimated axonal bulk and CSF volume from quantitative volumetric MRI imaging of the brain and combined these measurements to derive NfL-adjustment “weight”, used to multiply measured CSF NfL concentrations. We assessed clinical utility of this adjustment by evaluating correlations of raw, or adjusted NfL values with MS severity, defined as speed of accumulation of neurological disability and measured by the Multiple Sclerosis Disease Severity Scale (MS-DSS). Data are from patients who provided informed consent and were enrolled in IRB approved studies.

Results Unadjusted baseline NfL offers nearly zero predictive value (ρ=0.010, p=0.864, n=285), while MRI-adjusted baseline NfL has significantly higher predictive utility related to subsequent disability progression (ρ=0.261, p <0.0001, n=285).

Conclusions

Upon adjusting for an estimate of total axonal bulk, baseline NfL concentration offers greater predictive value related to MS progression as measured by the MS-DSS model. This work was funded by the NIAID Division of Intramural Research.

Authors/Disclosures
Jonathan Phillips PRESENTER	Jonathan Phillips has nothing to disclose.
Ruturaj Masvekar, PhD (National Institutes of Health)	Dr. Masvekar has nothing to disclose.
Peter Kosa, PhD (NIH/NINDS)	Dr. Kosa has nothing to disclose.
	No disclosure on file
Ann Weideman	No disclosure on file
Bibiana Bielekova, MD, FAAN (Neuroimmunological Diseases Section/NIAID/NIH)	Dr. Bielekova has received research support from National Institutes of Allergy and Infectious Diseases. Dr. Bielekova has received intellectual property interests from a discovery or technology relating to health care. Dr. Bielekova has received publishing royalties from a publication relating to health care.

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