Clinical and MRI correlates of CSF neurofilament light chain levels in relapsing and progressive MS

Damasceno, Alfredo; Carneiro, Rafael; Moraes, Adriel S.; Boldrini, Vinícius O.; Quintiliano, Raphael Patrício Silva; Silva, Verônica Almeida de Paula Galdino da; Farias, Alessandro S.; Brandão, Carlos Otávio; Damasceno, Benito Pereira; Santos, Leonilda Maria Barbosa dos; Cendes, Fernando

doi:10.1016/j.msard.2019.02.004

Cited by 21 publications

(29 citation statements)

References 24 publications

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“…Sellebjerg et al [62] measured CSF NfL levels in 26 patients with PPMS, 26 with SPMS, and 24 healthy controls and observed higher values in cases with active progressive MS in comparison with those with inactive progressive MS, thus supporting the role of NfL in distinguishing active vs. inactive cases. These data further confirm the specific association between NfL concentration and active disease at sampling, which has a significant impact on axonal damage [61] . Partially divergent data emerged according to a recent meta-analysis of case-control studies, where three times higher CSF NfL levels were observed in 158 patients with progressive MS in comparison with healthy controls, although significantly lower values were detected in progressive vs. relapsing cases.…”

Section: Nfl In Progressive Mssupporting

confidence: 79%

“…Different studies further support this hypothesis. Damasceno et al [61] analysed CSF NfL values in consecutive patients with MS, including 32 subjects with RRMS and 15 with progressive MS, and correlated NfL values with radiological and clinical variables. Interestingly, NfL levels were significantly increased in patients with RRMS in association with cortical lesions and relapses, whereas they were not different in patients with progressive MS in comparison with healthy controls.…”

Section: Nfl In Progressive Msmentioning

confidence: 99%

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Neurofilament light chain in demyelinating conditions of the central nervous system: a promising biomarker

Bozzetti¹,

Ferrari²,

Gajofatto³

et al. 2020

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Neurofilaments are the major structural proteins of the neuronal cytoskeleton and are classified according to molecular weight into heavy, intermediate, and light chains. They are released into the interstitial fluid and cerebrospinal fluid (CSF) as a consequence of axonal damage. In particular, the light chain (NfL) represents the most abundant and soluble subunit and has been demonstrated to be increased in the CSF of patients with inflammatory, degenerative, vascular, or traumatic injuries in correlation with clinical and radiological activity. Similar results have been obtained measuring serum NfL with high-sensitivity single-molecule array, which enables reliable and repeatable measurement of the low NfL concentrations in serum. In particular, CSF and serum NfL values are strongly correlated in patients with multiple sclerosis (MS) and have been demonstrated to be increased in patients with MS and clinically isolated syndromes (CIS) in accordance with clinical and radiological activity. NfL levels increase in patients with a recent relapse and seem to predict cognitive impairment, longterm outcome, and conversion of CIS to MS. The few available data on patients with other demyelinating diseases suggest that NfL levels are also increased in neuromyelitis optica spectrum disorders and related conditions in correlation with attack severity, suggesting that axonal damage may occur in these disorders. We herein report and discuss published data on the role of NfL as a possible predictor of disease activity, clinical outcome and treatment response in patients with demyelinating conditions of the central nervous system.

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Section: Nfl In Progressive Mssupporting

confidence: 79%

Section: Nfl In Progressive Msmentioning

confidence: 99%

Neurofilament light chain in demyelinating conditions of the central nervous system: a promising biomarker

Bozzetti¹,

Ferrari²,

Gajofatto³

et al. 2020

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“…Recently, both CSF and serum NfL measurements have been shown to correlate not only with current but also with previous clinical and MRI activity in RRMS. 22 , 23 Although assessments of disease activity (i.e., CSF NfL testing and clinical and radiologic assessments) were deemed to take place within a similar time frame, no predefined time intervals were set for this real-word study. This may explain the lack of association between CSF NfL measurements and some clinical and MRI measures evaluated in our study.…”

Section: Discussionmentioning

confidence: 99%

CSF neurofilament light chain testing as an aid to determine treatment strategies in MS

Reyes

Smets

Holden

et al. 2020

Neurol Neuroimmunol Neuroinflamm

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ObjectiveTo evaluate the use of CSF neurofilament light chain (NfL) measurements in clinical practice as well as their effect on treatment strategies and outcomes in patients with MS.MethodsThis was an observational cohort study of patients with MS who had a CSF NfL measurement between December 2015 and July 2018 as part of their routine clinical care. Treatment strategies were classified as “No Treatment/No Escalation” (no treatment or no escalation of treatment) or “Treatment/Escalation” (first-line injectable/oral disease-modifying therapies (DMTs), highly active DMTs, or treatment escalation). Change in Expanded Disability Status Scale (EDSS) scores was evaluated after 1-year follow-up.ResultsOf 203 patients with MS, 117 (58%) had relapsing-remitting MS. Disease activity was most frequently indicated by elevated CSF NfL (n = 85), followed by clinical (n = 81) and MRI activity (n = 65). CSF NfL measurements were independently associated with clinical (p = 0.02) and MRI activity (p < 0.001). Of those with elevated CSF NfL as the only evidence of disease activity (n = 22), 77% had progressive MS (PMS). In patients with PMS, 17 (20%) had elevated CSF NfL as the sole indicator of disease activity. Elevated CSF NfL resulted more frequently in Treatment/Escalation than normal CSF NfL (p < 0.001). Median EDSS change at follow-up was similar between patients receiving No Treatment/No Escalation and Treatment/Escalation decisions (p = 0.81).ConclusionsCSF NfL measurements informed treatment strategies, alongside clinical and MRI measures. CSF NfL levels were the only indicator of disease activity in a subset of patients, which was more pronounced in patients with PMS. Elevated CSF NfL was associated with more Treatment/Escalation strategies, which had an impact on EDSS outcomes at 1 year.

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“…Several studies have shown that NF-L is elevated in the blood and CSF of newly diagnosed MS patients and that this is correlated with disease severity and prognosis [21,[97][98][99]. NF-L is also elevated during disease activity such as a clinical relapse of new lesions on MRI [100,101]. This makes NF-L an attractive diagnostic biomarker in MS although its specificity does not allow differentiation from MS mimics like neuromyelitis optica spectrum disorders or other neuroinflammatory disorders [102,103].…”

Section: Multiple Sclerosismentioning

confidence: 99%

Neurofilaments: The C-Reactive Protein of Neurology

et al. 2020

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Neurofilaments (NFs) are quickly becoming the biomarkers of choice in the field of neurology, suggesting their use as an unspecific screening marker, much like the use of elevated plasma C-reactive protein (CRP) in other fields. With sensitive techniques being readily available, evidence is growing regarding the diagnostic and prognostic value of NFs in many neurological disorders. Here, we review the latest literature on the structure and function of NFs and report the strengths and pitfalls of NFs as markers of neurodegeneration in the context of neurological diseases of the central and peripheral nervous systems.

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Clinical and MRI correlates of CSF neurofilament light chain levels in relapsing and progressive MS

Cited by 21 publications

References 24 publications

Neurofilament light chain in demyelinating conditions of the central nervous system: a promising biomarker

Neurofilament light chain in demyelinating conditions of the central nervous system: a promising biomarker

CSF neurofilament light chain testing as an aid to determine treatment strategies in MS

Neurofilaments: The C-Reactive Protein of Neurology

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