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Blood Neurofilament Light Chain: The Neurologist’s Troponin?, 2020, Thebault et al

Discussion in 'Other health news and research' started by Hutan, Aug 4, 2021.

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  1. Hutan

    Hutan Moderator Staff Member

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    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700209/#B47-biomedicines-08-00523

    Abstract
    Blood neurofilament light chain (NfL) is a marker of neuro-axonal injury showing promising associations with outcomes of interest in several neurological conditions. Although initially discovered and investigated in the cerebrospinal fluid (CSF), the recent development of ultrasensitive digital immunoassay technologies has enabled reliable detection in serum/plasma, obviating the need for invasive lumbar punctures for longitudinal assessment.

    The most evidence for utility relates to multiple sclerosis (MS) where it serves as an objective measure of both the inflammatory and degenerative pathologies that characterise this disease.

    In this review, we summarise the physiology and pathophysiology of neurofilaments before focusing on the technological advancements that have enabled reliable quantification of NfL in blood. As the test case for clinical translation, we then highlight important recent developments linking blood NfL levels to outcomes in MS and the next steps to be overcome before this test is adopted on a routine clinical basis.​


    Canadian team (Thebault, Booth, Freedman) on the development of techniques to quantify a marker of nerve damage.
     
    Last edited: Aug 4, 2021
    Hutan, Aug 4, 2021
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  2. Hutan

    Hutan Moderator Staff Member

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    This is an interesting paper, not least because having a method to evaluate neuronal damage in neurological conditions like MS and Alzheimers is a game changer. For example:
    NfL was measured in a recent Italian study of Long Covid, but was only identified in 1 out of the 10 cases. It does degrade over time, so it is possible that if there was nerve damage at Long Covid onset, it could have disappeared by the time of the 6 month evaluation.


    The neurofilament light chains aren't the only possible marker of nerve damage. Note the peripherin - in the peripheral nervous system. Perhaps that could tell us if there is peripheral nerve damage without having to biopsy everywhere to find it?
     
    Hutan, Aug 4, 2021
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  3. Hutan

    Hutan Moderator Staff Member

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    47. Ameres M., Brandstetter S., Toncheva A.A., Kabesch M., Leppert D., Kuhle J., Wellmann S. Association of neuronal injury blood marker neurofilament light chain with mild-to-moderate COVID-19. J. Neurol. 2020 doi: 10.1007/s00415-020-10050-y. [PMC free article]

    We don't have a thread for the Ameres paper - I'll make one as it looks relevant.
    Here: Association of neuronal injury blood marker neurofilament light chain with mild-to-moderate COVID-19, 2020, Ameres et al
     
    Last edited: Aug 4, 2021
    Hutan, Aug 4, 2021
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  4. Hutan

    Hutan Moderator Staff Member

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    I reckon there's a study idea there - looking for those markers of nerve damage, prospectively in e.g. in an acute Covid-19 or EBV cohort, and during an exercise challenge.
     
    Hutan, Jul 11, 2024
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  5. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    Or retrospectively, in a cohort not biased by looking for NLC, i.e. the ME Biobank at CureME. If it has not been used it would be a good sample - ME/CFS, normals and MS all documented and available blinded.
     
    Jonathan Edwards, Jul 11, 2024
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  6. Hutan

    Hutan Moderator Staff Member

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    Yes, there's just the issue of nerve damage perhaps only occurring early after onset, so perhaps it wouldn't be picked up in the people who have established ME/CFS by the time they make it to the biobank.
     
    Hutan, Jul 11, 2024
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  7. FMMM1

    FMMM1 Senior Member (Voting Rights)

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    I think this [Blood neurofilament light chain (NfL)] was the test used in the high profile study linking EBV (virus) to MS [US Army recruits - blood/plasma samples]. It does illustrate why it was difficult to accurately diagnose early stage MS i.e. prior to the rollout of this test.
     
    FMMM1, Jul 12, 2024
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  8. Trish

    Trish Moderator Staff Member

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    Can you provide a link?
     
    Trish, Jul 12, 2024
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  9. EndME

    EndME Senior Member (Voting Rights)

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    It's the Ascherio paper discussed here. I don't think that diagnosis of early MS has in any way changed even with NfL tests being available.
     
    EndME, Jul 12, 2024
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  10. SNT Gatchaman

    SNT Gatchaman Senior Member (Voting Rights)

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    This paper came out today —

    Neurofilament Light Chain Serum Levels Mirror Age and Disability in Secondary Progressive Multiple Sclerosis
    Leila Husseini, MD, Jakob Jung, Natalie Boess, Niels Kruse, Stefan Nessler, Christine Stadelmann, Imke Metz, Michael Haupts, Martin S. Weber

    OBJECTIVES
    To assess neurofilament light chain serum (sNfL) levels in patients with secondary progressive multiple sclerosis (SP-MS).

    METHODS
    Using a single molecule array, we analyzed sNfL levels in a cross-sectional cohort study of 153 patients with SP-MS hospitalized for rehabilitation in a clinic specialized in the care for patients with multiple sclerosis (MS). In addition, we investigated the correlation of disease activity with sNfL levels in 36 patients with relapsing-remitting MS (RR-MS).

    RESULTS
    Mean sNfL levels in patients with SP-MS were consistently elevated when compared with age-matched controls and patients with RR-MS. In SP-MS, age dependency of sNfL levels was pronounced, whereas patients with RR-MS younger than 41 years without recent disease activity were not distinguishable from age-matched healthy controls. In a multivariate analysis, clinical disability was a risk factor for elevated sNfL levels in SP-MS, whereas no correlation with comorbidities, such as cardiovascular disease, diabetes mellitus, smoking status, or vitamin D serum levels, could be detected.

    DISCUSSION
    These findings highlight that measurement of sNfL levels represents a useful tool to assess the extent of neuroaxonal damage as a surrogate for clinical progression in patients with SP-MS, when age and disease activity as major confounders are taken into account.

    Link | PDF (Neurology Neuroimmunology & Neuroinflammation)
     
    Last edited: Jul 12, 2024
    SNT Gatchaman, Jul 12, 2024
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  11. Hutan

    Hutan Moderator Staff Member

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    It highlights that the NfL seems to only be present when the neuronal damage is present, it doesn't seem to stay in the system long. So negative results in ME/CFS don't rule out the possibility that neuronal damage occurs at onset, and during PEM.
     
    Hutan, Jul 12, 2024
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  12. EndME

    EndME Senior Member (Voting Rights)

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    This little table, taken from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7198337/ seems quite useful as it summarizes the current research on NfL for different diseases. Similarly this table shows that there is a large overlap between healthy controls and different illnesses. There is also an interactive tool which tells you reference ranges per diseases, age and where the sample is taken from. It seems useful: https://mybiomarkers.shinyapps.io/Neurofilament/ (it's from this publication https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(24)00005-7/fulltext).

    So I don't think you'll ever get anything close to a "biomarker" or much separation, but I think a large study showing differences and perhaps untangling when NfL values seem to be higher in LC and ME/CFS seems very useful. I would also add GFAP and the others to the mix since those have also appeared to be elevated in numerous studies. It also seems that blood measurements tell you less than CSF measurements, so I'm not sure how much use an existing biobank would be.
    [​IMG]
     
    Last edited: Jul 13, 2024
    EndME, Jul 13, 2024
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