Exploring CSF neurofilament light as a biomarker for MS in clinical practice; a retrospective registry-based study

Abstract

Background: Neurofilament light (NFL) has been increasingly recognized for prognostic and therapeutic decisions. Objective: To validate the utility of cerebrospinal fluid NFL (cNFL) as a biomarker in clinical practice of relapsing-remitting multiple sclerosis (RRMS). Methods: RRMS patients ( n = 757) who had cNFL analyzed as part of the diagnostic work-up in a single academic multiple sclerosis (MS) center, 2001–2018, were retrospectively identified. cNFL concentrations were determined with two different immunoassays and the ratio of means between them was used for normalization. Results: RRMS with relapse had 4.4 times higher median cNFL concentration (1134 [interquartile range (IQR) 499–2744] ng/L) than those without relapse (264 [125–537] ng/L, p < 0.001) and patients with gadolinium-enhancing lesions had 3.3 times higher median NFL (1414 [606.8–3210] ng/L) than those without (426 [IQR 221–851] ng/L, p < 0.001). The sensitivity and specificity of cNFL to detect disease activity was 75% and 98.5%, respectively. High cNFL at MS onset predicted progression to Expanded Disability Status Scale (EDSS) ⩾ 3 ( p < 0.001, hazard ratios (HR) = 1.89, 95% CI = 1.44–2.65) and conversion to secondary progressive MS (SPMS, p = 0.001, HR = 2.5, 95% CI = 1.4–4.2). Conclusions: cNFL is a robust and reliable biomarker of disease activity, treatment response, and prediction of disability and conversion from RRMS to SPMS. Our data suggest that cNFL should be included in the assessment of patients at MS-onset.

Antisense Oligonucleotide Therapy: From Design to the Huntington Disease Clinic

“…This is further evidenced by the transient increase in the CSF NfL. CSF NfL is currently being studied as a marker in neurodegenerative diseases [ 100 – 102 ] and pre-clinical animal models of HD [ 103 ]. NfL has also been found in higher concentrations in plasma and CSF of HD and pre-HD patients and is thought to be related to neuronal cell death [ 104 ].…”

Emerging Biomarkers of Multiple Sclerosis in the Blood and the CSF: A Focus on Neurofilaments and Therapeutic Considerations

“…On the other hand, different studies documented a significant relationship between age and CSF, serum, and plasma NfL in MS [ 40 , 156 , 278 , 287 ]. The association between NfL and gender is also controversial; most studies found no relationship between CSF and serum NfL and sex [ 40 , 271 , 287 , 288 ]. On the other hand, a cohort reported higher serum NfL levels in females [ 289 ], while according to other studies, CSF NfL concentrations were more prominent in male patients [ 290 , 291 ].…”

“…Ultimately, in case of uncertainty, measurement of NfL might be utilised as a complementary examination to distinguish patients at risk of developing CDMS from non-converters. In addition to identifying CIS patients with a risk of future conversion, higher baseline CSF NfL is associated with disease severity [ 263 ], future EDSS progression and conversion to SPMS [ 288 , 290 ]. Data in the literature suggests that not baseline [ 263 ] serum NfL but the change in its level indicates future conversion to SPMS [ 301 ].…”

“…According to cross-sectional studies, high baseline CSF NfL levels correlate with high baseline EDSS [ 156 , 285 ] and future EDSS progression [ 276 , 288 , 290 ]. Somewhat contradictory to this data are the results of other studies that confirmed the correlation between baseline CSF [ 298 ], serum [ 289 ] and plasma [ 313 ] NfL levels and baseline EDSS but failed to link them to future EDSS and disability progression.…”

“…Baseline CSF NfL levels are associated with baseline [ 285 ], and future Gd+ lesions [ 299 ]. Similarly, CSF NfL levels were shown to correlate not just with the presence of Gd+ lesions [ 185 , 291 , 321 ], but with the number of Gd+ lesions [ 288 , 322 ] as well. In contrast, another study found a correlation only between CSF NfL levels and the presence, but not the number of Gd+ lesions [ 157 ].…”