An Exploration of Real-world Serum Neurofilament Light Chain Measurement and Rate of ALSFRS-R Decline
Cate Ledoux1, Micah Hamilton1, Cassandra Holmes1, Nicholas Streicher1, Shakti Nayar1
1Department of Neurology, Georgetown University
Objective:
Our aim was to evaluate whether measures used to assess ALS progression in the clinical setting, specifically changes in the Revised ALS Functional Rating Scale (ALSFRS-R) questionnaire, are meaningfully associated with serum neurofilament light chain (NfL) levels measured by a commercial laboratory.
Background:
Serum NfL, a neuronal cytoplasmic protein, has been proposed as a prognostic marker in ALS. Controlled prospective observational studies have supported single molecule (SIMOA) assay-quantified serum NfL as a predictor of survival and ALSFRS-R rate of change. Given the commercial availability of electrochemiluminescence (ECLIA) serum NfL testing, it may be useful to further explore the utility of NfL alongside existing clinical assessments.
Design/Methods:
We conducted an IT-based data extraction to review ECLIA serum NfL tests (Dec 2022-Jan 2025) ordered by Neuromuscular providers for patients in our ALS clinic, and their ALSFRS-R scores at the time of testing (n=25). When available, we also reviewed the ALSFRS-R score from a clinic visit within approximately 180 days (M=120, SD=43) after testing (n=10).
A Spearman rank correlation was calculated for serum NfL levels and patients’ ALSFRS-R scores at the time of NfL testing. This was also performed for serum NfL levels and ALSFRS-R rate of decline, computed in points per month.
Results:
Although we did not find a correlation between serum NfL levels and one-time ALSFRS-R scores (ρ = -0.1327, p > 0.5), we found a statistically-significant monotonic correlation between serum NfL and a greater rate of decline in ALSFRS-R score (ρ = 0.6810, p < 0.05).
Conclusions:
Our findings indicate a strong positive correlation. As ALSFRS-R rate of decline increases, the commercially-available serum NfL value also increases. This emphasizes the potential value of tracking serum NfL in the clinical setting alongside ALSFRS-R, providing a possible complementary method of quantifying progression. Future research can examine serum NfL relative to other clinical assessments or medication usage.
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