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Elevated Neurofilament Light Chain in Cerebrospinal Fluid and Plasma Reflect Inflammatory MRI Activity in
Keld-Erik Byg1,2,3, Helle H Nielsen1,2,4, Tobias Sejbaek2,5,6
1Department of Neurology, Odense University Hospital, J.B. Winsloewsvej 4, 5000 Odense, Denmark.
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 (n = 20) median 2304 pg/mL (interquartile range (IQR) 630-19,612) compared to 426 pg/mL (IQR 261-571) in extra-neurologic sarcoidosis patients (n = 20) and 336 pg/mL (IQR 194-402) in healthy controls (n = 11) (p = 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 (p = 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 (p = 0.009 and p = 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.
Insights
Neurofilament light chain (NFL) is elevated in cerebrospinal fluid and plasma of neurosarcoidosis patients, indicating disease activity. Higher NFL levels correlate with MRI-detected inflammation, suggesting NFL as a potential biomarker.
Area of Science:
- Neurology
- Biomarker Discovery
- Inflammatory Diseases
Background:
- Axonal damage releases neurofilament light chain (NFL) into bodily fluids.
- Neurosarcoidosis is a rare inflammatory disease affecting the central nervous system (CNS).
- Identifying reliable biomarkers for neurosarcoidosis activity is crucial for patient management.
Purpose of the Study:
- To evaluate neurofilament light chain (NFL) as a biomarker for disease activity in neurosarcoidosis.
- To compare NFL levels in patients with neurosarcoidosis, extra-neurologic sarcoidosis, and healthy controls.
- To correlate NFL levels with MRI findings of CNS inflammation.
Main Methods:
- Measurement of NFL levels in cerebrospinal fluid (CSF) and plasma.
- Comparison of NFL levels across neurosarcoidosis, extra-neurologic sarcoidosis, and healthy control groups.
- Assessment of MRI scans for enhancing lesions to grade CNS inflammation.
Main Results:
- Significantly higher NFL levels were observed in the CSF and plasma of neurosarcoidosis patients compared to controls.
- CSF NFL levels in neurosarcoidosis patients were median 2304 pg/mL vs. 426 pg/mL (extra-neurologic) and 336 pg/mL (controls).
- Plasma NFL levels in neurosarcoidosis patients were median 28.2 pg/mL vs. 6.2 pg/mL (extra-neurologic) and 7.1 pg/mL (controls).
- Higher NFL levels correlated with moderate/severe CNS inflammation on MRI.
- CSF and plasma NFL cut-offs demonstrated high sensitivity and specificity for distinguishing neurosarcoidosis.
Conclusions:
- NFL is a sensitive biomarker for disease activity in neurosarcoidosis.
- Elevated NFL levels in CSF and plasma reflect CNS inflammation in neurosarcoidosis.
- NFL shows potential for monitoring disease progression and treatment response in neurosarcoidosis.
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