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Axonal Degeneration: More Intense in the Early Stages of MS?

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  • Axonal Degeneration: More Intense in the Early Stages of MS?

    Eur Neurol
    . 2020 Sep 21;1-9.
    doi: 10.1159/000510116. Online ahead of print.

    Axonal Degeneration Independent of Inflammatory Activity: Is It More Intense in the Early Stages of Relapsing-Remitting Multiple Sclerosis Disease?

    Vedat Cilingir 1, Muhammed Batur 2
    Affiliations expandAbstract


    Background: This study aimed to investigate whether there are differences in the axonal degeneration rate between patients in the early years of relapsing-remitting multiple sclerosis (RRMS) disease and RRMS patients in their later years.

    Methods: The early-stage RRMS patients (EMS) group had 65 patients whose duration of disease was within 3 years from the date of the first attack. The late-stage RRMS patients (LMS) group had 69 patients whose duration of disease was within the range of 3-10 years from the date of the first attack. In addition, a control group was composed of 32 healthy subjects. Peripapillary retinal nerve fiber layer (RNFL) thickness was monitored with spectral-domain OCT in all included patients for approximately 3 years.

    Results: The annual RNFL atrophy rate (aRNFLr) in the EMS group was -1.246 0.778 μm/year, the aRNFLr in the LMS group was -0.898 0.536 μm/year, and the aRNFLr was -0.234 0.154 μm/year in the control group (p < 0.001). The aRNFLr in the EMS group was significantly higher than the aRNFLr in the LMS group (p = 0.01). The aRNFLr was not associated with MRI activity or the condition of having an attack. There was a correlation between Expanded Disability Status Scale (EDSS) progression and aRNFLr in both the EMS and LMS patient groups (r = -0.471, p < 0.001, and r = -0.567, p < 0.001, respectively).

    Conclusion: The axonal degeneration rate is faster in RRMS patients in the first years of the disease than in later years. In addition, axonal degeneration occurs independently of inflammatory activity. Axonal degeneration is correlated with disability progression, but not with inflammatory findings, such as clinical episodes and MRI activity.
    Dave Bexfield
    ActiveMSers

  • #2
    Is axonal damage the same as what is referred to as the silent "smouldering" MS? I would have thought the axonal damage would have increased more with time, especially once RRMS becomes spms. I wonder if examination of brain tissue post mortem would have demonstrated that correlation? The study looked at retina scans, as I understood it.

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    • #3
      I continued to be perplexed by the finding of this paper so a little digging help me read more of findings: the researchers followed msers for 3 yrs period of time and they compared new msers (<3yrs) with old msers (3-10 yrs since 1st attack). Im not a science person, but my impression is that their conclusion about axonal damage occurs more at beginning of disease is overly broad based on length of time they observed msers, the manner observed (retinal fibers only??), and lack of info in abstract about type of disease modifying drugs being used during this time. I dont know, am I crazy? Retinal meaurement is helpful to monitor disease but is this conclusion to broad?

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      • #4
        Suebee, it appears MS starts doing its damage way early, flipping any notion that letting the disease be and taking a "wait and see" in the early stages is unwise. Other neuros on the internet have been discussing this study as well....

        https://multiple-sclerosis-research....ing-into-papa/
        Dave Bexfield
        ActiveMSers

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        • #5
          Thanks Dave for the direction. I didn’t understand the distinction between demyelination and axonal loss, and considered them almost synonymous. I looked at link you suggested and more, and my glib understanding now is that scientists know there is a connection between inflammation
          , demyelination, and neurodegeneration, and have been busy with studies like this one you posted, trying to tease it out . This is great. This type of thinking will lead to better therapies, and in a timely fashion. The term neuroprotective comes up a lot, and this term is more than anti inflammatory or just upregulating T cells. Thanks for highlighting these distinctions for me through this study. It’s so significant.

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