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

Abstract

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.

Inflammatory profiles in plasma and cerebrospinal fluid of patients with neurosarcoidosis

“…The median duration of symptoms in NS patients was eight months before inclusion, and four patients were on immunosuppressive medication. None of the NS patients had severe comorbidity (Byg et al, 2021). Eighteen patients (90%) had systemic sarcoidosis, and 2 (10%) had isolated NS.…”

“…To focus on the CNS disease, NS patients with polyneuropathy and diseases that could cause similar symptoms to NS were excluded. NS patients with CNS disease and small fiber neuropathy were accepted (Byg et al, 2021). The neurology departments at Odense University Hospital recruited healthy controls (HC) among patients admitted with unspecific symptoms without any signs of neurological or systemic inflammatory diseases and with normal CSF and MRI scans.…”

“…The neurology departments at Odense University Hospital recruited healthy controls (HC) among patients admitted with unspecific symptoms without any signs of neurological or systemic inflammatory diseases and with normal CSF and MRI scans. Some of the baseline data have been published previously (Byg et al, 2021).…”

“…Supratentorial meningeal enhancement, infratentorial meningeal enhancement, parenchymal enhancement, and enhancing lesions in the cervical spine, thoracic spine, lumbar spine, or cauda equina give one point each. A score of 0 points was graded no enhancement, 1-2 points were graded mild enhancement, and a score of 3-6 points was graded moderate/severe enhancement (Byg et al, 2021).…”

“…In the contrast-enhancing lesions on MRI, eight patients had no enhancement, five patients were grouped as mild enhancement, and seven patients were grouped as moderate/severe enhancement. (Byg et al, 2021).…”