Neurofilament light chain and oligoclonal bands are prognostic biomarkers in radiologically isolated syndrome

Abstract

The prognostic role of cerebrospinal fluid molecular biomarkers determined in early pathogenic stages of multiple sclerosis has yet to be defined. In the present study, we aimed to investigate the prognostic value of chitinase 3 like 1 (CHI3L1), neurofilament light chain, and oligoclonal bands for conversion to clinically isolated syndrome and to multiple sclerosis in 75 patients with radiologically isolated syndrome. Cerebrospinal fluid levels of CHI3L1 and neurofilament light chain were measured by enzyme-linked immunosorbent assay. Uni- and multivariable Cox regression models including as covariates age at diagnosis of radiologically isolated syndrome, number of brain lesions, sex and treatment were used to investigate associations between cerebrospinal fluid CHI3L1 and neurofilament light chain levels and time to conversion to clinically isolated syndrome and multiple sclerosis. Neurofilament light chain levels and oligoclonal bands were independent risk factors for the development of clinically isolated syndrome (hazard ratio = 1.02, P = 0.019, and hazard ratio = 14.7, P = 0.012, respectively) and multiple sclerosis (hazard ratio = 1.03, P = 0.003, and hazard ratio = 8.9, P = 0.046, respectively). The best cut-off to classify cerebrospinal fluid neurofilament light chain levels into high and low was 619 ng/l, and high neurofilament light chain levels were associated with a trend to shorter time to clinically isolated syndrome (P = 0.079) and significant shorter time to multiple sclerosis (P = 0.017). Similarly, patients with radiologically isolated syndrome presenting positive oligoclonal bands converted faster to clinically isolated syndrome and multiple sclerosis (P = 0.005 and P = 0.008, respectively). The effects of high neurofilament light chain levels shortening time to clinically isolated syndrome and multiple sclerosis were more pronounced in radiologically isolated syndrome patients with ≥37 years compared to younger patients. Cerebrospinal fluid CHI3L1 levels did not influence conversion to clinically isolated syndrome and multiple sclerosis in radiologically isolated syndrome patients. Overall, these findings suggest that cerebrospinal neurofilament light chain levels and oligoclonal bands are independent predictors of clinical conversion in patients with radiologically isolated syndrome. The association with a faster development of multiple sclerosis reinforces the importance of cerebrospinal fluid analysis in patients with radiologically isolated syndrome.

Serum neurofilament light as a biomarker in progressive multiple sclerosis

“…In patients with Alzheimer disease and amyotrophic lateral sclerosis, increasing mean serum concentrations occur months or years before the emergence of the first clinical manifestations. 35,36 Similarly, an increased CSF NfL concentration in radiologically isolated syndrome is a risk factor for later transition to clinically definite MS. 37,38 Recent results from clinical trials in progressive MS accord with those in relapsing-remitting disease (table 1) and suggest that the concentration of NfL is associated with concurrent disease activity and long-term disease outcome in all forms of MS. In placebo-controlled phase 3 trials of fingolimod and siponimod, baseline plasma NfL concentrations were higher in patients with Gd+ lesions at baseline compared with those without Gd+ lesions.…”

Cerebrospinal Fluid Neurofilament Light Chain Is Associated with Kynurenine Pathway Metabolite Changes in Multiple Sclerosis

“…NFL seems to be a robust marker of ongoing disease activity in pwMS. Moreover, NFL levels correlate well with conversion to clinically definitive MS [15,16], increased number of relapses, confirmed disability worsening, treatment and MRI outcomes [17], spinal cord and brain atrophy [4,18,19], and different clinical forms such as radiologically isolated syndrome [20], clinically isolated syndrome (CIS) ( [21], relapsing-remitting MS (RRMS) [16,22,23], and primary progressive MS (PPMS) [24]. NFL levels correlate significantly with the presence of gadolinium enchancing lesions and T2 lesion load [20].…”

Neurofilament light chain as a biomarker in neurological disorders

“…It has been found that a higher CSF NfL concentration is an independent risk factor for the development of MS in RIS patients, although it has minor relevance (hazard ratio = 1.03, 95% CI 1.01-1.05 p = 0.003) in comparison to other prognostic markers such as CSF IgG oligoclonal bands (OCB) (hazard ratio = 8.9, 95% CI 1.04-75.6 p = 0.046). [39] The ability of CSF NfL to predict conversion to MS in CIS patients is controversial. While some authors have reported higher CSF NfL values at the baseline in CIS patients who were later diagnosed with MS,[S8] some others have reported contrasting findings.…”