74 Comments
founding
Aug 16Liked by Gavin Giovannoni

This article clearly lays out the role of EBV versus potential triggers in the development of MS.

I had mono in college and only in the past year (in my late 50s) did I develop (or rather, recognize) serious-enough symptoms to seek care and get dx’ed with PPMS.

The past 4 years have been exceedingly stressful: pandemic, Trump (I’m in US), George Floyd (I’m in Minneapolis), my wife of 33 years developed radiation-induced osteosarcoma of the maxilla (which promptly recurred): I believe these things finally exhausted my neuro reserve. I haven’t had Covid (knowingly), so could not develop the bias to confirm!

I have “denial bias:” how reliably have I ignored my array of MS symptoms or attributed them to aging or stress.

Writing this comment has taken me ages: I am dismayed at my cognitive deterioration and yet … comforted to have a believable explanation for my befuddlement, rather than “I guess I was wrong to think I was smart.”

Expand full comment
Aug 20Liked by Gavin Giovannoni

We need a word for the stress related health effects of Trump.

Expand full comment
founding
Aug 20Liked by Gavin Giovannoni

Ha ha, we DO. Although I see him more as a symptom than a malady.

Expand full comment
founding
Aug 19Liked by Gavin Giovannoni

Hi Judy, in states here. It has been incredibly stressful. My former business partner is in Rochester. (We practiced in California.) I completely understand your feelings. It has been like being dragged through the proverbial knothole. I’m so sorry about your wife. Oh dear, that indeed drains reserves. I hope you find some care and relief because it is all so difficult (understatement). Sending you both lots of good thoughts.💕

Expand full comment
founding
Aug 20Liked by Gavin Giovannoni

Thank you, Italien! You are a stranger to me, yet I am genuinely comforted by your words. I am so fortunate in some ways — eg, no struggle nor delay in getting diagnosed w/MS, and in getting strong DMT Ocrevus (although I am not sure it will benefit me). Best wishes in all, to you.

Expand full comment
Aug 16Liked by Gavin Giovannoni

Very pleased to see you address this issue Prof G. Lots of psMS appear to be favouring the idea that either COVID or the COVID vaccine caused their MS and it can be quite frustrating to read this, albeit understandable given the need to attribute blame. Both my brother and I have MS and we both had EBV at University. He was diagnosed 7 years later with MS and I was diagnosed 8.5 years later. That virus has a lot to answer for!

Hope you are keeping as well as can be. Take good care.

Expand full comment
Aug 16Liked by Gavin Giovannoni

Thank you for this article. I have a huge history of viral infections, trauma, migraines and depression since childhood and then a bad case of Glandular Fever at 17years in first year at university. Followed by more stress and trauma, Viral Labyrinthitis, post viral fatigue, anxiety, depression, carpel tunnel, swollen ulcerated tongue during pregnancy, lots of pain all over my body, raynauds, memory problems, tinnitus yet I have been told by my more than one Neurologist that all of this has nothing to do with MS. Neurologists have dismissed even looking at my symptoms since I had a “normal” neurological exam! What even is normal- we are all very different with MS at the end of the day!

So very frustrating as now I believe I have had MS for a very long time. If only the NHS looked at us all as individuals instead of the black and white view of just treating a disease or not!

Expand full comment
founding
Aug 16Liked by Gavin Giovannoni

This is very interesting indeed, it's definitely something we've talked about between myself and my parents.

I was straight-A's at GCSE (16 years old).

During my time in 6 form my academic performance dropped off markedly and I ended up with straight B's at A-level having dropped my 4th A level (Further Maths) (18 years old).

My parents both noted changes in my behaviour which wouldn't necessarily be put down to puberty. As my mother taught GCSE & A-level sciences her whole career she was pretty attuned to teenage behavioural changes, these changes were outside normal expected changes in teenagers. My father had been a GP so, again, he knew about expected behavioural ranges.

I struggled with concentration a little at university but graduated with a 2:2 - again grades dropping. In my first "proper" job I started very well, having to teach myself IT networking stuff. But over time during my career, my ability to teach myself dropped off. I self-taught myself a lot of programming to begin with and have, on and off, worked professionally as a programmer my whole life. But cog fog has been the bain of my life.

Then I had my "first" episode in 2001 at the age of 25. My GP refused to even refer me to a private neuro as he'd already decided I was a massive hypochondriac. Luckily I was able to go over his head, my dad ended up doing the initial neuro exam - all the standard stuff - he booked me in for the private neuro appointment, private neurologist insisted on an immediate MRI which I got to see and my brain was lit up like a Christmas tree - CLEARLY this weren't the first lesions.

When did I get EBV? I was exposed to it in primary school, one of my classmates caught glandular fever and she was off for ages with it. A class of 28 of us, 2 of us boys (not her) that I know of have since been diagnosed with MS. Maybe I was exposed again later, I've no idea. I know the other guy's MS appeared after mine and his prognosis and evolution have been far worse than mine.

I didn't see any relief from cognitive fog (on Copaxone 2005 - 2016 then Tecfidera) until 2018 after I'd been on Tecfidera for a year or two and the cog fog started to lift. It came back after I came of Tec (lymphopenia) and stayed while I was on Ocrevus. I switched to Mavenclad in 2022 and in the last year or so, again, cog fog has started to lift, to the point where I'm now back programming again.

As for COVID I'm lucky enough to be resident in Spain, we moved to the Canary Islands after the first (and only) lockdown as the islands were handling the pandemic much better. I'm still here. Me and my family still mask in public, still have the boosters when offered, still mask on public transport. There's a LOT of evidence that COVID (even omicron) crosses the blood-brain barrier in the olfactory nerve, causes lesions and can allow latent EBV to become active - I'm not happy taking that risk. I live in semi-isolation, it works for me but I know I'm one of the very, very, very lucky ones because MOST PwMS have to expose themselves to the outside world on a constant basis and - well COVID is "over"...

Expand full comment
founding
Aug 19Liked by Gavin Giovannoni

Hi Simon, I also wear a mask and am very careful. Believe it or not, here in the US, they are banning masks in certain states. It is simply irresponsible on every level. I don’t understand it at all. But I’m a masker no matter!

Expand full comment
Aug 16Liked by Gavin Giovannoni

I'm very sure that pandemic stress contributed to drawing down my neurologic reserves enough for the MS to show symptoms. But my first MRI (months after symptoms started due to pandemic healthcare scheduling issues) had uncountable old lesions. Literally, they stopped counting after a few dozen, and it seems like that kind of damage would have started well before COVID. I'm lucky in that my symptoms are pretty mild.

I honestly have no idea what the initial trigger was; I never had mono/EBV that I know of (which doesn't mean I never had it). I do suspect my illness has a very very very long tail.

I have all the COVID vaccines and boosters, including the extra ones immune-compromised folks could get.

Expand full comment
Aug 16Liked by Gavin Giovannoni

Will (pwms)

Very good article and I agree entirely. I developed MS at the age of 26, 7 1/2 years after getting Glandular fever.

I do however think I can link the initial onset of symptoms to a sporting head injury when I was 14!

Expand full comment
founding
Aug 19Liked by Gavin Giovannoni

Will, I wonder how much head injury/concussion may have to do with our disease. For those of us that were athletic, some of us sustained some massive concussions. ?

Expand full comment
Aug 20Liked by Gavin Giovannoni

I think I've seen a bit of research on this; not a new question. I fell on my head a couple times and used my head the wrong way during football. But how many normal kids got banged around or had an accident?

Expand full comment
author

Head injury increases one's risk of getting MS. However, it is only a small increase in risk.

Expand full comment
Aug 16Liked by Gavin Giovannoni

I had glandular fever aged 11. Diagnosed with MS at 23. I recall funny sensations during my teenage years, including cold and heavy legs, and pins and needles in my fingers. While I did have a hepatitis vax about a month before diagnosis because i was planning on travel, I had already noticed other symptoms leading up to the first episode such as Llhermite’s sign.

When I was diagnosed in December’99, one of the junior doctors asked me if I had had glandular fever. 25 years later we’re still talking about this. Science moves very slowly!!

Expand full comment
Aug 16Liked by Gavin Giovannoni

I had EBV at age 14 and was off school for 6 weeks, completely exhausted but didn’t have the sore throat normally associated with EBV.

My MS systems began at age 21 which fits in with the time frame Prof G has mentioned.

I went to the doctors many times with numbness symptoms from age 21 then was diagnosed at 29, this was 20 years ago.

Expand full comment
Aug 16Liked by Gavin Giovannoni

As someone who had no obvious symptoms until a day after the first covid vaccine then had my first symptom of PPMS 2 months later while out for a run I find this reassuring because people around me are constantly blaming the vaccine. I think I have had symptoms on and off for 20 years. I even made my GP refer me to a neurologist(who didn't find anything but did offer me an MRI, I wish I had taken him up on the offer) as I was convinced I had a problem coming from my cerebellum, I am now told by my physio and MS nurse I have lesions in my cerebellum.

Expand full comment
Aug 16Liked by Gavin Giovannoni

Wish I could sit down over tea and discuss my history.

Post Mavenclad in 2022 (completed 2021) I was taken off the antivirals I need to keep EBV from reacting.

I had a six week reactivation March through May. Not tested but very obvious. For the first time in my history, I had actual EBV symptoms thanks to Mavenclad giving my immune system a boost. It is not NEW EBV after an IRT though. It is IDENTIFIABLE EBV. Due to good docs, mine was identified BEFORE the IRT when it didn’t look like EBV.

I’ve had many reactivations since 2015 and they were simply six weeks of balance, both leg weakness and extensive fatigue “relapse, no lesion seen”. In 2018 I converted to gradually worsening over nine months - fatigue, cognitive fatigue, balance and leg strength. Called progression - secondary progressive. Although I had no symptoms of EBV, my naturopathic doctor convinced my gp to send me for a massive amount of bloodwork (basically a naturopathic neurotoxicity panel). Lo and behold I had markers of current EBV reactivation. My gp wondered if antivirals would do anything (okay, I begged him, because holistic antiviral treatment wasn’t doing anything).

Within 1-2 weeks mobility was back. EBV causes vestibular difficulties that affect brain and balance and fatigue levels for me. After Mavenclad, add sore throat, swollen lymph nodes and more because my immune system cared again.

This is long. Sorry. But once I had had EBV reactivation after Mavenclad I started to progress again, even though I had seemed to beat it.

Then end of August I got mild/moderate Covid. After which I had a dual relapse, one old lesion and one “new” one.

Covid did not cause the new lesion. I had a well timed MRI two weeks before I got Covid and the new lesion was already there. I hadn’t relapsed yet. Covid did cause a mass of inflammation of some sort which kicked up the relapse as well as ten months of PASC.

Did my EBV reactivation earlier in the year cause the new lesion? Maybe? 🤷‍♀️

My leg weakness during an EBV reactivation is NOT initially actual weakness. (My only mobility lesion is right sided weakness which I have rehabbed extensively). I can stand in place safely at the beginning. But legs buckle when I walk and can’t support me. To start it’s a vestibular issue. Enter walker and wheelchair which eventually would lead to actual leg weakness, no lesion involved. I see this ALL THE TIME in those treated with B cell depletors who are “getting worse” with stable MRI (due to what I do with The MS Gym). Maybe not EBV. But the system trying to fight SOMETHING that is not identifiable.

When our immune systems get tipped towards inflammatory rather than regulatory, comorbid conditions get missed. It has been years since I’d had a fever or had a cold. Fighting to get treatment for an UTI that has no pain - I just start falling down.

Finally, being unable to keep EBV in check was the start of progression for me. An antiviral slows replication only. It’s not a cure. But it leaves margin for my immune system to keep working somewhat properly. On an antiviral, I do get sick, get fevers, and don’t get resistant infections. Off the antiviral, fevers disappear, infections start, I get rosacea, then eventually walker and wheelchair.

I suspect this is impacting a cohort of those with secondary. I think it may be due to poor viral control genetics. The MS severity gene is in an area of viral control and I do have that homozygous variant. I also wonder if this is why Covid is a neuro nightmare for me?

Note that this goes beyond EBV causing MS - no clue about that. But it definitely in my own life affects MS trajectory. And due to my history, it was definitely obvious that Covid didn’t cause the lesion.

How many with new onset MS post Covid had a clean or no-change MRI just prior to getting Covid?

Expand full comment

In addition to EBV connection to MS, HSV-1 may be involved as well.

Alzheimer’s disease and multiple sclerosis: a possible connection through the viral demyelinating neurodegenerative trigger (vDENT). Boukhvalova et al., 2023.

https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2023.1204852/full

The lack of success in a number of recent clinical trials of immune- or amyloid-targeting therapeutics emphasizes our incomplete understanding of their etiology and pathogenesis. Evidence is accumulating that infectious agents such as viruses may contribute either directly or indirectly. With the emerging recognition that demyelination plays a role in risk and progression of AD, we propose that MS and AD are connected by sharing a common environmental factor (a viral infection such as HSV-1) and pathology (demyelination). In the viral DEmyelinating Neurodegenerative Trigger (vDENT) model of AD and MS, the initial demyelinating viral (e.g., HSV-1) infection provokes the first episode of demyelination that occurs early in life, with subsequent virus reactivations/demyelination and associated immune/inflammatory attacks resulting in RRMS. The accumulating damage and/or virus progression deeper into CNS leads to amyloid dysfunction, which, combined with the inherent age-related defects in remyelination, propensity for autoimmunity, and increased blood-brain barrier permeability, leads to the development of AD dementia later in life. Preventing or diminishing vDENT event(s) early in life, thus, may have a dual benefit of slowing down the progression of MS and reducing incidence of AD at an older age.

Expand full comment
author

When you apply causation theory to HSV-1 & HSV-2 and MS the evidence does not hold up.

Expand full comment
Aug 16·edited Aug 16Liked by Gavin Giovannoni

Very pleased that you have addressed Covid-19 and the vaccines as playing a role in triggering symptoms or relapses.

I had the Astra zeneca vaccinations 1 year before my first relapse. In this year, I developed recurring headaches whilst felt abnormal. I also experienced Covid-19 for the first time 3-4 months before my first clinical relapse. During having Covid-19, I experienced very strong headaches as a symptom. The few months preceding the relapse, I was also under a lot of stress trying to write my clinical report as a part of my masters. I remember being up late at night, not getting much sleep, constantly worrying myself and placing a huge amount of pressure on this. During that past year I had to try to navigate this masters and placements whilst in the lockdown and uncertainty triggers anxiety and stress for me. As an Art Psychotherapist, I also consider the history and effects of trauma on the nervous system and subsequently the high levels of cortisol triggered when the nervous system is elevated when experiencing levels of distress or anxiety. I may have had MS lying dormant for a long time, I have never been checked for EBV. But I did feel that a combination of all of these events triggered my relapse and MS to be active.

Thank you for discussing this, it’s been at the forefront of my thinking a lot since being diagnosed.

Expand full comment
Aug 16Liked by Gavin Giovannoni

it is human nature to search for simple answers for complex problems. thank you Prof G for clearly and calmly laying out why the simple answer is the wrong one here

Expand full comment
Aug 16Liked by Gavin Giovannoni

I had mono when I was 17, and after that, I never felt the same. I had a lot of fatigue after that, although my tests all came back normal. I wasn't diagnosed until I was 36.

Expand full comment
Aug 16Liked by Gavin Giovannoni

I had weak legs and lower back pain in my early teens and the 'hug' in my early 20's. I wasn't diagnosed till my 40's when I had a severe relapse whilst in bed with a flu type virus 12 years ago.

Expand full comment
Aug 16Liked by Gavin Giovannoni

Glandular fever at 15, first MS symptoms at 22, diagnosed in 1997 at 32. I almost got accepted onto the ATARA EBV trial (Excluded due to having had a melanoma 17 years previously) and anyway this trial was discontinued due to inconclusive results. But I believe there are other trials still going ahead on EBV-related treatments, yes?

Expand full comment
founding
Aug 16Liked by Gavin Giovannoni

The frexalimab trials look very interesting...

Expand full comment
Aug 16Liked by Gavin Giovannoni

Well that one's new to me! I'll look it up, thanks.

Expand full comment
Aug 21Liked by Gavin Giovannoni

Well, there you go, they're running a frexalimab trial at the Austin Hospital in Melbourne. It's a six hour drive but looks very promising ... I have registered my interest. Thanks, Simon!

Expand full comment
Aug 16Liked by Gavin Giovannoni

Just before my A levels in 1978 I developed whole body pruritis for 3 to 4 weeks. It was horrendous. I saw GPs, specialists, no one knew what it was. They decided it was exam anxiety & dosed me up on benzos. When I was dx in 1994, Professor MacDonald at Queen Sq said my lesions were at least a decade old, so I suspect the pruritus attack was MS.

Expand full comment