Research: viral infection and evidence is with EBV

Zaadstra et al.  Selective association of multiple sclerosis with infectious mononucleosis. Mult Scler. 2008;14(3):307-13.

Previous studies have suggested an association between MS and infectious mononucleosis (IM) but data on the exact strength of this association or its selectivity have been conflicting. In this study the investigators evaluated the association between MS and a variety of common childhood infections and afflictions in a large population-based case-control study involving 2,877 MS cases and 2,673 controls in the Netherlands.

They examined the frequency of different common infections and afflictions before the age of 25 and the age at which they occurred, using a self-administered questionnaire. The Odds ratios (ORs) for the occurrence of a variety of clinically manifest common childhood infections including rubella, measles, chicken pox and mumps before the age of 25 for MSers versus controls ranged between 1.14 and 1.42, values similar to those for irrelevant probe variables used to reveal recall bias.

In contrast, the OR for clinically manifest IM in MS cases versus controls, corrected for demographic variables, was 2.22 (95% confidence interval 1.73 – 2.86; P < 0.001). The average age of onset of IM in the population of MSers (16.5 years) did not differ from controls (16.8 years). Their data confirm previous much smaller studies to show that the risk for MS is significantly enhanced by prior IM, and extend those previous data by showing that this association is far stronger than with other common childhood infections or afflictions.

Ramagopalan et al.  Association of infectious mononucleosis with multiple sclerosis. A population-based study. Neuroepidemiology. 2009;32:257-62.

BACKGROUND: Genetic and environmental factors have important roles in MS susceptibility. Several studies have attempted to correlate exposure to viral illness with the subsequent development of MS. Here in a population-based Canadian cohort, the researchers investigated the relationship between prior clinical infection or vaccination and the risk of MS.

METHODS: Using the longitudinal Canadian database, 14,362 MS index cases and 7,671 spouse controls were asked about history of measles, mumps, rubella, varicella (Chicken pox) and infectious mononucleosis as well as details about vaccination with measles, mumps, rubella, hepatitis B and influenza vaccines. Comparisons were made between cases and spouse controls.

RESULTS: Spouse controls and stratification by sex appear to correct for ascertainment bias because with a single exception we found no significant differences between cases and controls for all viral exposures and vaccinations. However, 699 cases and 165 controls reported a history of infectious mononucleosis (p < 0.001, corrected odds ratio 2.06, 95% confidence interval 1.71-2.48). Females were more aware of disease history than males (p < 0.001).

CONCLUSIONS: The data further confirms a reporting distortion between males and females. Historically reported measles, mumps, rubella (German Measles), varicella (Chicken pox) and vaccination for hepatitis B, influenza, measles, mumps and rubella are not associated with increased risk of MS later in life. A clinical history of infectious mononucleosis is conspicuously associated with increased MS susceptibility. These findings support studies implicating Epstein-Barr virus in MS disease susceptibility, but a co-association between MS susceptibility and clinically apparent infectious mononucleosis cannot be excluded.

“There have been many studies reporting the link between certain viruses and MS. But when looked at using larger sample sizes most viruses have fallen by the wayside. The exception appears to be Epstein Barr Virus (EBV) which causes glandular fever or infectious mononucleosis If you have glandular fever and got the virus in adolescence it increases your risk (using the data above about twice as likely) of developing MS. Search on the BLOG for EBV and infectious mononucleosis and there are loads of posts as a pet subject of Prof G.”

CoI: Studies were my members of Team G or from the partners of people from Team G

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  • As you I believe in a virus triggered / caused MS.
    The theory I am about to present is mainly based on the Varizella Zoster Virus (VZV) but it can also apply to any other (maybe undiscovered) virus.
    So the first thing you see in MS is a "misbehavior" in the immune system. But I think the immune system is doing something we don't understand.

    But why?

    I guess that a virus triggers the immune system to overreact. .
    The virus in charge must be one which has a certainly high "rate of plague" (can't find a proper english term, german: Durchseuchungsrate) like Varizella Zoster- , Ebstein Barr -, Morbilli-virus, etc. as this could be an explanation why no one is safe from MS and females have a higher risk than males.
    It is known that VZV can rest in the dorsal root ganglion for years before it awakes again and causes shingles in adults. Shingles are the symptom of the VZV traveling alongside the peripheral nerves. But what if VZV decides to move along the nerves into the brain or is stopped moving alongside the peripheral nerves and hit the other direction?

    As the virus travels into the brain it needs some form of energy to survive. This energy might be provided by the myelin or the nerve impulses.
    Now we have a infection of the brain. This is a high emergency state for the immune system and causes an alarm.
    The immune system is now attacking the myelin to be able to attack the virus.
    The rest is known as MS.

    Are there any pro arguments?

    – Interferone ß1 a/b: also work as an antiviral agent, but only seem to work in about 20% of all MSers
    – University of Gothenburg, 1997 "Acyclovir treatment of relapsing-remitting multiple sclerosis": small study with a VZV specific antiviral agent (Acyclovir) with a positive outcome. I can't rate the quality of this study.
    – Mitoxantrone: also has antiviral characteristics, but as it works mainly as an immunesuppressant the effects maybe reversed.
    – VZV positive results of liquor analysis in MS patients.
    – Zoster-Encephalitis causes similar symptoms like MS (don't know about the MRI presentation)

    After all, most of the existing MS treatments have antiviral characteristics. But most of the drugs only seems to work in a certain rate of MSers.

    – It could be easily falsified if some of the mentioned viruses need myelin or nerve impulses as a source of energy.

  • An old post had this: "Although the majority of children with MS are seropositive for remote EBV exposure, EBV is not obligatory for MS development in children"

    In January a commenter had said "in me the MS chicken seems to have come before the EBV egg"
    Prof G replied "I may be changing my position on EBV being the only trigger for MS. I beginning to suspect that other viruses can do it as well. … Wait and see"

    Please post more information about this.

    If different viruses can trigger MS, is it possible that bacterial infections can do it too?

    What are the consequences of EBV not being the only trigger? It seems to me that 'multiple causes' is not very different from 'unknown cause'

  • I know my experience has little statistical significance, but I certainly didn't have a full blown mono attack, although I'm aware most of the population shows signs of having been infected; it could've hidden as a low grade cold/flu – most of my life I have been in robust health. For what it's worth!

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