American Military show that MS starts years before it shows itself

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Migration data suggests that people contract the MS trigger before the aga of 15 but we know from clinical studies that it often doesn’t show itself for years later. However it appears that this grumbles on for many years before it rears its ugly head.

The American Mitltary is a big beast full of healthy young people who get good medical check-ups. They have their bloods taken and stored.

Using this resource it was shown previously that soldiers who developed multiple sclerosis, became infected with EBV before their MS showed itself. In this report they can find evidence of inflammatory damage in the blood, six years before diagnosis. This is called the Prodrome.

Serum Neurofilament Light Chain Levels in Patients With Presymptomatic Multiple Sclerosis. Bjornevik K, Munger KL, Cortese M, Barro C, Healy BC, Niebuhr DW, Scher AI, Kuhle J, Ascherio A. JAMA Neurol. 2019 Sep 13. doi: 10.1001/jamaneurol.2019.3238. [Epub ahead of print]

IMPORTANCE:Unrecognized demyelinating events often precede the clinical onset of multiple sclerosis (MS). Identification of these events at the time of occurrence would have implications for early diagnosis and the search of causal factors for the disease.

OBJECTIVE:To assess whether serum neurofilament light chain (sNfL) levels are elevated before the clinical MS onset.

DESIGN, SETTING, AND PARTICIPANTS: Nested case-control study among US military personnel who have serum samples stored in the US Department of Defense Serum Repository. Serum samples were collected from 2000 to 2011; sNfL assays and data analyses were performed from 2018 to 2019. We selected 60 case patients with MS who either had 2 samples collected before onset (mean follow-up, 6.3 years) or 1 sample collected before and 1 after onset (mean follow-up, 1.3 years), among 245 previously identified case patients. For each case, we randomly selected 1 of 2 previously identified control individuals matched by age, sex, race/ethnicity, and dates of sample collection. The sample size was chosen based on the available funding.

EXPOSURES: Serum NfL concentrations measured using an ultrasensitive single-molecule array assay (Simoa).

MAIN OUTCOMES AND MEASUREMENTS:Log-transformed sNfL concentrations in case patients and control individuals compared using conditional logistic regression and linear mixed models.

RESULTS: Mean age at baseline was 27.5 years, and 92 of 120 participants (76.7%) were men. Serum NfL levels were higher in case patients with MS compared with their matched control individuals in samples drawn a median of 6 years (range, 4-10 years) before the clinical onset (median, 16.7 pg/mL; interquartile range [IQR], 12.6-23.1 pg/mL vs 15.2 pg/m; IQR, 10.3-19.9 pg/mL; P = .04). This difference increased with decreasing time to the case clinical onset (estimated coefficient for interaction with time = 0.063; P = .008). A within-person increase in presymptomatic sNfL levels was associated with higher MS risk (rate ratio for ≥5 pg/mL increase, 7.50; 95% CI, 1.72-32.80). The clinical onset was associated with a marked increase in sNfL levels (median, 25.0; IQR, 17.1-41.3 vs 45.1; IQR, 27.0-102.7 pg/mL for presymptomatic and postonset MS samples; P = .009).

CONCLUSIONS AND RELEVANCE: The levels of sNfL were increased 6 years before the clinical MS onset, indicating that MS may have a prodromal phase lasting several years and that neuroaxonal damage occurs already during this phase.PMID: 31515562 DOI: 10.1001/jamaneurol.2019.3238

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12 comments

  • If this is true shouldn’t everyone with a risk factor Be automatically screened? For example in my case my mother died of ms at the nice old age of 51. At age 30, scared I’d get it too, I went to a neurologist. He did a brain MRI, which was fine, and said i ne we needed one again. Ten years later boom, MS. Imagine how different the outcome would have been if he had screened for NFL. What if, as with family history of cancer, everyone could be proactively screened, starting at age 15! Is there any chance doctors will start doing this?

    • I suspect that neurofilament could supercede MRI, which is relevant as the safety of repeated enhancing lesion MRI has been questioned as the particles accumulate in the brain for a while. I know ProfG has used this to test to spot a relapse when MRI couldn’t find the lesion. So when you can’t see the forest fire from twenty miles away, you can often see the smoke. The same logic.

      One question is how well does serum neurofilament link to spinal fluid neurofilament? Whilst the Swiss group have inferred there is a clear and good correlation, this was not supported by our data. CSF is the better source to test. But I guess if you can see it in the blood it will in the brain. Perhaps we need to do a prospective study and screen all soldiers for neurofilament, then do MRI to see when lesions accumulate and are seen.

      This study needs to be repeated, I remember ProfG telling me about wanting to do this very study many, many years ago, I wonder if he asked them and they went off and did it. However there is no monopoly on ideas and two people can have the same idea at the same time.

      Maybe we could do this for the British or Swedish Army as it would be important to replicate.

      The cost of the screen is not a huge amount, which NDG runs. Could this be a triiger to treat and stop MS arriving. I was surprised to hear that neurafilament it is not a routine (low cost) test in the US..An opportunity that will surely be plugged.

  • So a kid with 6 years old with ms

    Got infected with Ebv on the day that he or she was born with virtually no memory b cells so no reservoir for Ebv to infect

    Absolute numbers of B-cell subsets by age group (/mL blood).

    0-1 m 1-6 m 6-8m 18m -4y 4y-8y 8-12 y 12-18y

    CD27þ IgD 1 (0–4) 6 (1–13) 19 (7–57) 48 (20–93) 42 (11–103) 34 (13–72) 33 (12–69)

    B-cell subpopulations in children: National reference values

    doi: 10.1002/iid3.26

      • Age also modifies the CSF profile at disease onset.8 Patients <11 years of age have a higher percentage of neutrophils in CSF and are less likely to show OCBs or elevated IgG index than patients with onset between ages 11 and 17 years.4,8

        No ocb (where are the b cells and the ebv driving them?)

        neutrophils? Ebv?

        doi:10.1002/ana.24364.

    • maybe the EBV is passed to the kid while in the womb, or it could come from the father.
      Some trigger will set if off.

      EBV sounds really invasive.

      • ” Epstein-Barr virus (EBV), originally recognized for its ability to infect and transform lymphocytes, is now clearly understood to infect epithelial cells as part of its normal cycle of persistence in a human host, and under some circumstances, the virus may infect T cells, natural killer cells, smooth muscle cells, and possibly monocytes as well.” From https://jvi.asm.org/content/81/15/7825 DOI: 10.1128/JVI.00445-07 It’s a nasty virus. I doubt any EBV infected B memory cells remember anything important about other infections.

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