Tuesday, 8 March 2016

ResearchSpeak: viral infections and relapse

Could reactivation of herpes viruses be triggering relapses? #MSBlog #MSResearch #ResearchSpeak

"The three cases below of MSers with brainstem lesions and evidence of varicella-zoster virus (VZV or chicken-pox virus) reaction in their CSF is interesting. We have to assume the diagnostic results are real and not false-positives. Believe it or not that when using very sensitive tests such as PCR you frequently get false-positive results. Could it be that the acute MS activity reactivated the virus that typically lies dormant in sensory neurones? Or could reactivation of the virus have triggered the MS to become active?"

"We are aware that relapses in MS are frequently triggered by infections; about a third of relapses are known to be preceded by infections. These are typically viral infections.We have no idea how many relapses are triggered by reactivation of dormant viral infections, such as VZV, CMV and EBV. The latter is one of the hypotheses underpinning the viral hypothesis of autoimmunity, i.e. that viral infections drive autoimmunity by stimulating or boosting the immune system that allows the autoimmune cells to be easily triggered to damage self. How do we test this hypothesis? It may have been tested already, but we don't know it. Does interferon beta and interferon alpha, which are antiviral agents work in MS by suppressing viral infections? Some of the original data on exogenous viral infections (colds, flu, etc.) suggests that interferon-beta does not reduce these types of infections, but we don't have data on the impact of these agents on reactivation of persistent viral infections, in particular EBV. As part of the Charcot Project we are hoping to get some information on this."  

"Anecdotally, I have looked after a few patients who have had a strong temporal relationship between herpes virus reactivation and relapse. Two of these patients noticed a major reduction in their relapses when they were put onto long term antiviral drugs by their virologists. Interestingly, their relapses were stereotypical suggestive of a MS lesion been reactivated at the same site in the spinal cord. The latter may therefore have simply been a pseudorelapse due to conduction block in a demyelinated pathway rather than a true relapse. This is why it is so hard to do research in this area; sorting out pseudorelapses from true relapses is not easy."


Torkildsen et al. Detection of varicella-zoster virus DNA during medullary and brainstem relapses in multiple sclerosis. BMJ Case Rep. 2016 Feb 23;2016. pii: bcr2016214555. doi: 10.1136/bcr-2016-214555.

We describe three cases of patients with concomitant acute medullary or brainstem multiple sclerosis (MS) lesions and detectable spinal fluid varicella-zoster virus DNA. Herpes simplex virus PCR was also positive in two of the patients. One patient was re-punctured 2 weeks following the relapse, with negative results. The PCR findings greatly delayed correct diagnosis and treatment in all three patients. Based on our cases, we propose that inflammatory medullary and brainstem lesions could result in viral leakage, and possibly viral reactivation, from destroyed sensory neurons, yielding false-positive cerebrospinal fluid PCR results. As this can have diagnostic and therapeutic consequences, further studies are warranted to evaluate the clinical relevance of these findings.

5 comments:

  1. Have RRMS. I had a left sided facial palsy, like bells palsy about 18 months ago. I felt dizzy. I took antiviral as it may have been caused by HSV, no steroids, stayed in bed, tried to not get stressed, slept a lot. It cleared up in two weeks. I was not on a DMD at the time.

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  2. How is the second Charcot project coming along now funding has been reached?

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  3. "Interestingly, their relapses were stereotypical suggestive of a MS lesion been reactivated at the same site in the spinal cord."

    I don't understand this - could you please explain what you mean by "stereotypical" in this case?

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  4. Are there any guidelines GP's re MS and infections? I spoke to my GP recently and he said we treat MS patients the same as the general population with regards to treating infections.

    I am on a DMD and know infections can trigger relapses. If I get a bacterial infection I want to start a broad scope antibiotic the same day and get urine sample sent to lab. I know with viruses it's different.

    Surely there are some guidelines for GP's on this?

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  5. I know several pwMSers who have been infected with Herpes Simplex or Herpes Zoster.
    They always report that every time the cited viruses become active they end up having relapses same, either by reactivation of injuries such as new injuries ...
    So Will besides EBV other viruses could act presenting immune cells antigens?

    If this evidence would be a similarity of MS with Guillain-Barré syndrome...

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