Elevated Neurofilament Light Chain in Cerebrospinal Fluid and Plasma Reflect Inflammatory MRI Activity in Neurosarcoidosis

• Main Authors: Keld-Erik Byg, Helle H. Nielsen, Tobias Sejbaek, Jonna Skov Madsen, Dorte Aalund Olsen, Nina Nguyen, Astrid Kindt, Jakob Grauslund, Zsolt Illes, Torkell Ellingsen
• Format: Article
• Language: English
• Published: MDPI AG 2021-02-01
• Series: Brain Sciences
• Subjects: neurofilament light chain; biomarker; neurosarcoidosis; cerebrospinal fluid; MRI
• Online Access: https://www.mdpi.com/2076-3425/11/2/238

Background: Damage to axonal cells releases neurofilament light chain (NFL) into the cerebrospinal fluid and plasma. The objective of this study was to investigate NFL as a potential biomarker of disease activity in neurosarcoidosis. MRIs were graded according to enhancing lesions at different central nervous system (CNS) sites. Results: In cerebrospinal fluid, levels of NFL were higher in neurosarcoidosis patients (<i>n</i> = 20) median 2304 pg/mL (interquartile range (IQR) 630–19,612) compared to 426 pg/mL (IQR 261-571) in extra-neurologic sarcoidosis patients (<i>n</i> = 20) and 336 pg/mL (IQR 194–402) in healthy controls (<i>n</i> = 11) (<i>p</i> = 0.0002). In plasma, levels of NFL were higher in neurosarcoidosis patients median 28.2 pg/mL (IQR 11.5–49.3) compared to 6.2 pg/mL (IQR 4.3–8.2) in extra-neurologic sarcoidosis patients and 7.1 pg/mL (IQR 6.2–9.0) in healthy controls (<i>p</i> = 0.0001). Levels in both cerebrospinal fluid and plasma were higher in neurosarcoidosis patients with moderate/severe enhancement than patients with mild enhancement on MRI (<i>p</i> = 0.009 and <i>p</i> = 0.005, respectively). To distinguish neurosarcoidosis patients from extra-neurologic patients and healthy controls, a cut-off level of 630 pg/mL in cerebrospinal fluid had 94% specificity and 79% sensitivity, while a cut-off level of 11.4 pg/mL in plasma had 97% specificity and 75% sensitivity. Conclusions: NFL levels in cerebrospinal fluid and plasma are significantly higher in neurosarcoidosis patients compared to extra-neurologic patients and healthy controls, and the levels correlate to the extent of inflammation on MRI.