Neurofilament Light Chain Levels in Cerebrospinal Fluid and Plasma in Neurosarcoidosis

Keld-Erik Byg¹, Tobias Sejbaek ², Helle Nielsen ³, Zsolt Illes ⁴, Jonna Skov Madsen ⁵, Dorte Olsen ⁶ and Torkell Ellingsen ¹, ¹Department of Rheumatology, Odense University Hospital, Denmark, Odense, Syddanmark, Denmark, ²Department of Neurology, Odense University Hospital; Department of Clinical Research, University of Southern Denmark, Denmark, Odense, Syddanmark, Denmark, ³Department of Neurology, Odense University Hospital, Department of Clinical Research, University of Southern Denmark, Denmark, Odense, Syddanmark, Denmark, ⁴Department of Neurology, Odense University Hospital, Department of Clinical Research, University of Southern Denmark, Denmark, Odense, Midtjylland, Denmark, ⁵Department of Biochemistry and Immunology, Lillebaelt Hospital, Vejle, Department of Regional Health Research, University of Southern Denmark, Denmark, Vejle, Syddanmark, Denmark, ⁶Department of Biochemistry and Immunology, Lillebaelt Hospital, Vejle, Denmark., Vejle, Syddanmark, Denmark

Meeting: 2019 ACR/ARP Annual Meeting

Keywords: neurosarcoidosis and biomarkers

Session Information

Date: Sunday, November 10, 2019

Title: Miscellaneous Rheumatic & Inflammatory Disease Poster I: Fibroinflammatory & Granulomatous Disorders & Therapies

Session Type: Poster Session (Sunday)

Session Time: 9:00AM-11:00AM

Background/Purpose:

Neurofilament Light Chain (NFL) is an emerging biomarker that is specific for neuronal and axonal damage/degeneration but unspecific regarding the origin of destruction. NFL has been suggested as biomarker in neurological diseases. No study has so far examined relation between neurosarcoidosis (NS) and NFL.

The purpose is to compare NFL levels in plasma and cerebrospinal fluid (CSF) in sarcoidosis patients with NS compared to healthy controls (HC).

Methods:

Plasma and CSF from consecutive biopsy positive sarcoidosis patients with suspected NS and/or relapsing NS (n=19). Based on WASOG-criteria, patients were characterized into two groups: highly probable NS (n=14) and a non-NS group (n=5). Results were compared to the HC (n=11). NFL concentrations were analyzed using Single Molecular Array (SIMoA) from Quanterix. NFL Levels above 807.5pg/ml in CSF and 13.0 pg/ml in plasma were considered elevated. Group medians were compared using Kruskal-Wallis and Mann-Whitney tests. Range is given in brackets.

Results: The average mean age of NS patients was 45 years (23-59) and disease duration median 5.5 (2-259) months. Of the patients with NS 79 % (n=11) initially presented with CNS symptoms. The remaining patients: one developed NS after 4 months under glucocorticoid treatment, one had chronic NS with symptom aggravation under immunosuppression and one had skin sarcoidosis with relapse of NS. Elevated serum angiotensin converting enzyme (ACE) was found in 14 % (n=2) and elevated plasma Interleukin-2 in 57 % (n=8). Abnormal MRI of brain was found in 50% (n=7) and medulla 21 % (n=3). Pleocytosis (LKC >5/ml) of the CSF was found in 79 % (n=11) and protein elevation in 79% (n=11). Oligoclonal bands were found in 21% (n=3). NFL was elevated in 64% (n=9) in plasma and 57% (n=8) in CSV.
The average mean age in the non-NS group was 45 years (26-60), and disease duration median 45 (11-272) months. 20% (n=1) had elevated ACE, 40% (n=2) had elevated IL-2. Median CSF NFL was significantly higher (p< 0.005) in NS (1537 pg/ml; 184-43961) compared to non-NS (426 pg/ml; 249-689) and HC (336 pg/ml; 81-499). Also, median plasma NFL level was significantly higher (p< 0.05) in NS (16.8 pg/ml; 4.8-191.8) compared to non-NS (9.2 pg/ml; 5.1-11.4) and HC (7.1 pg/ml; 3.0-10.9). Plasma and CSF NFL in NS patients was not found to be significantly different between NS patients with or without MRI pathology. No patient in non-NS group and HC group had abnormal NFL in plasma or CSV.

Conclusion:

Both plasma and CSF NFL were significantly higher in NS patients compared to non-NS patients and HC´s. Plasma and CSF NFL were elevated in 64% and 57% of NS patients, respectively, compared to none of the patients in non-NS or HC group. NFL could be related to extend of CNS affection, but our study was underpowered to demonstrate a significant different difference in NS patient with and without MRI and CSF abnormalities. This is the first study demonstrating elevation of NFL in both blood and CSF in patients with NS. Further studies are needed to evaluate the potential use of NFL as a biomarker supporting the diagnosis of NS, prognosis of the disease and if NFL could be used clinically to monitor response of immunological treatment.

Disclosure: K. Byg, Eli Lilly, 9; T. Sejbaek, Biogen, 9, Roche, 9; H. Nielsen, None; Z. Illes, None; J. Madsen, None; D. Olsen, None; T. Ellingsen, None.

To cite this abstract in AMA style:

Byg K, Sejbaek T, Nielsen H, Illes Z, Madsen J, Olsen D, Ellingsen T. Neurofilament Light Chain Levels in Cerebrospinal Fluid and Plasma in Neurosarcoidosis [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/neurofilament-light-chain-levels-in-cerebrospinal-fluid-and-plasma-in-neurosarcoidosis/. Accessed .

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