The prognostic value of CSF neurofilaments in multiple sclerosis at 15-year follow-up

Petzold, Axel

doi:10.1136/jnnp-2014-309827

Cited by 32 publications

(30 citation statements)

References 8 publications

(12 reference statements)

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“…Immunoassays for both NfL and NfH have been extensively published and have short-term and long-term prognostic value in various neurologic disorders. [2][3][4][5] The phase II riluzole trial in participants with early multiple sclerosis (MS) was a randomized, double-blind, placebo-controlled study assessing the putative neuroprotective effect of riluzole. The primary outcome of the trial, brain atrophy, was negative.…”

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confidence: 99%

Serum neurofilament is associated with progression of brain atrophy and disability in early MS

et al. 2017

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Objective: To investigate a potential effect of riluzole on serum neurofilaments (Nf) compared to placebo and the relationship between longitudinal clinical and MRI outcomes and serum Nf levels.Methods: Serum samples were obtained from participants enrolled in a randomized double-blind trial of neuroprotection with riluzole vs placebo as an add-on to weekly interferon-b (IFN-b)-1a IM initiated 3 months after randomization. Nf measurements were performed by ELISA and electrochemiluminescence immunoassay.Results: Longitudinal serum samples were available from 22 riluzole and 20 placebo participants over 24 months. There was no observed treatment effect with riluzole. Nf light chain (NfL) levels decreased over time (p 5 0.007 at 24 months), whereas the Nf heavy chain was unchanged (p 5 0.997). Changes in NfL were correlated with EDSS change (p 5 0.009) and neuropsychological outcomes. Brain volume decreased more rapidly in patients with high baseline NfL (p 5 0.05 at 12 months and p 5 0.008 at 24 months) and this relationship became stronger at 24 months (p 5 0.024 for interaction). Higher and increasing NfL predicted higher number of gadoliniumenhancing lesions (p , 0.001 for both). 1 They determine axonal caliber and transport, and during axonal injury can be measured in the CSF and blood. Immunoassays for both NfL and NfH have been extensively published and have short-term and long-term prognostic value in various neurologic disorders. 2-5The phase II riluzole trial in participants with early multiple sclerosis (MS) was a randomized, double-blind, placebo-controlled study assessing the putative neuroprotective effect of riluzole. The primary outcome of the trial, brain atrophy, was negative. 6 Our goal was to investigate a potential treatment effect on serum NfL and NfH and the longitudinal relationship between serum Nf levels and clinical and MRI outcomes.

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Serum neurofilament is associated with progression of brain atrophy and disability in early MS

et al. 2017

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“…37 In a 15-year follow-up study, higher levels of CSF Nf-L at baseline were associated with greater disability progression in relapsing-remitting multiple sclerosis (RRMS) patients. 38 Changes in concentrations while on treatment also have been linked to treatment response. 39 Additional markers are being explored actively, but most of the profusion of reports based on studies with smaller populations have later failed replication; Kroksveen et al 40 recently reported that from 188 proposed CSF MS biomarkers, only 10 (5%) have been successfully validated.…”

Section: Personalised Medicine For Multiple Sclerosis: Is It Needed?mentioning

confidence: 99%

Personalised medicine for multiple sclerosis care

2016

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Treatments with a range of efficacy and risk of adverse events have become available for the management of multiple sclerosis (MS). However, now the heterogeneity of clinical expression and responses to treatment pose major challenges to improving patient care. Selecting and managing the drug best balancing benefit and risk demands a new focus on the individual patient. Personalised medicine for MS is based on improving the precision of diagnosis for each patient in order to capture prognosis and provide an evidence-based framework for predicting treatment response and personalising patient monitoring. It involves development of predictive models involving the integration of clinical and biological data with an understanding of the impact of disease on the lives of individual patients. Here, we provide a brief, selective review of challenges to personalisation of the management of MS and suggest an agenda for stakeholder engagement and research to address them.

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“…1,2,7 In a recent study in 51 MS patients, it has been shown that higher CSF NfH values could prognosticate an unfavourable disease evolution during a follow-up time of 15 years. 3 Another study in 95 MS cases with a median follow-up time of 14 years could demonstrate that elevated CSF NfL levels were predictive of future physical disability. 10 More recently, a larger study in 259 patients (189 with relapsing-remitting MS and 70 with progressive MS) with a clinical follow-up time of median 6.5 years demonstrated that serum NfL was predictive of Expanded Disability Status Scale (EDSS) worsening over time, and higher serum NfL levels were associated with contrast enhancing and new/enlarging lesions seen on MRI.…”

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confidence: 99%

“…1,2 Neurofilaments (Nf), which are specific to neurons and axons, are to date the most promising markers to monitor neuro-axonal damage. 3 Nf belong to intermediate filament proteins and consist of three isotypes, which are a neurofilament light (NfL) chain of 68 kDa, a neurofilament intermediate (NfM) chain of 150 kDa, and a neurofilament heavy (NfH) chain of 190-210 kDa. 1 Evidence for increased Nf levels in MS mainly exists for NfL and NfH, whereas NfM has not been extensively studied so far.…”

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confidence: 99%

Are neurofilaments valuable biomarkers for long-term disease prognostication in MS?

Khalil

2018

Mult Scler

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The prognostic value of CSF neurofilaments in multiple sclerosis at 15-year follow-up

Cited by 32 publications

References 8 publications

Serum neurofilament is associated with progression of brain atrophy and disability in early MS

Serum neurofilament is associated with progression of brain atrophy and disability in early MS

Personalised medicine for multiple sclerosis care

Are neurofilaments valuable biomarkers for long-term disease prognostication in MS?

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