Professor Julia Newton: Research Presentation: Transcript and Video: November 2012

[Firestormm]

Apologies that it has taken me so long to type up the transcript to the presentation made by Newton at the Action For ME Annual General Meeting back at the end of November in 2012.

I referred originally to it here and we discussed it a bit on that thread. Newton covers all the research currently being conducted as well as past research and clinical treatment for - in the main - autonomic nervous system dysfunction, in her own inimitable style.

From the presentation:

Slide 24 – Looking forward:

MRC Medical Research Council

o Understanding the pathogenesis of autonomic dysfunction in CFS and its relationship with cognitive impairment
o Identifying the biological fingerprints of fatigue
o Understanding Muscle Dysfunction in ME/CFS – developing a drug Pre-Testing System
o A case controlled study exploring the qualitative experience of sleep, the roles of sleep architecture and patters of salivary cortisol in ME/CFS

Julia Newton:

"Looking forward, I am very pleased to say that in the recent round of applications for the CFS call from the MRC, in Newcastle we were very successful in securing £900,000 of the £1.5 million, ‘pot’.

So now we are in a very nice position to begin to understand what causes the autonomic dysfunction that seems to be so prevalent in CFS and how it relates to cognitive impairment. And what we are now able to do is do all of those investigations that I have highlighted, plus many more, in the same people – so we will be able to look in a whole-systems-way at what is the underpinning problems in people with CFS/ME.

We’ve also obtained a project where I am the co-investigator, and Dr Wan Ng is the principal investigator – he is an immunologist – to look at trying to identify an immunological biomarker for fatigue; and we’ve made an application to ME Research UK to try and allow us to straddle these two applications and make the very most out of both of them by maximising the samples we can take."

There was much in the talk that I found interesting about POTS for example and in relation to the muslce-gym where muscle cells are exercised in the lab to help determine and confirm the irregularities in our muscle function - as well as helping to determine viable treatments.

The sound quality - especially for the Q&A - was not the best and so I've had to summarise some of the questions asked for example because of a lack of microphones.

Usual caveats apply, namely that I can't guarantee the accuracy of my transcript, although you have links to the video and to the slides in order to compare.

Hope you enjoy as much as I have. You can of course follow developments in Newcastle from their Facebook page - though it's not wholly interactive but good for news in my 'umble opine.

Fire

 

[Sasha]

Thanks for doing this, Firestormm - what an enormous amount of work! But she's a major player in the UK so well worth knowing what she's doing.

 

[Sasha]

Still reading this, but, wow! They're exercising muscle tissue grown as cultures from CFS patients and measuring the lactic acid they produce. Eat that, psych lobby!

 

[Sasha]

They've done MRI studies showing a third of patients don't generate energy within the heart walls as they should, wow... proper science... wow...

 

[Shell]

Firestorm thank you for the hard work.

It is good to see some proper research done in the UK.

I do wish however that the good doc wouldn't equate NMH as if it were the only ANS symptom. I have POTS with a massive hike in BP. It does drop suddenly but only from the stroke high levels it can reach. Hyperadrenergic and combo POTs might not be as common as POTs with NMH but we do exist.
My memory, thought processes and language producation (and sometimes reception) is seriously naff. I worry that the narrow focus of Dr Newton's work in CFS will exclude those of us who have a different flavour of dysautonomia from being treated. As it is most doctors don't know what PoTs is - to have them think it must go along with hypotension is not helpful to a lot of us.

Her work on muslces is great and hopefully will filter through to the boxed in heads of docs around the country. There is more research underway it seems.
Funny how Julia Newton isn't a Dame

 

[Shell]

Aha, someone at the end asks about high BP - she thinks low BP folk don't get the attention they need. Ok I guess so, but those of us with hyper don't get much help either. But she does say it's dysautonomic.

Her talk of how sugar craving and a sense of a hypogl attack could be a drop in BP is interesting. As my son has type 1 I've tested my blood when this happens and it's always normal. However I know my BP does the hike and then the dive quite often so perhaps the hypo-feeling is that. Interesting.
I hope she gets more answers soon.


And thanks again Firebird

 

[Firestormm]

No worries peeps. I am pleased you all seem to think like I do that it was an encouraging talk.

After listening to Julia I have had to revise my own thinking about 'traditional' advice for someone who is feeling feint. Used to be that the advice was - I seem to recall - to put one's head between one's knees.

But I now think - having looked a little into it - that raising one's feet above one's head whilst lying down is probably better advice. Important to get blood into one's noggin and not take it away placing more strain on the heart.

Sorry. A little aside

And may I just say thanks to Simon for putting my efforts into pdf. for me. I don't have the technology or know-how I am afraid. Cheers matey

 

[barbc56]

Wow, Fire, I'm impressed. Now I have more reading to do!!!!!

Barb

 

[biophile]

Meanwhile, Klimas now attributes autonomic symptoms to "deconditioning" and is into physical rehabilitation?

http://www.mecfsforums.com/index.php/topic,14672.msg146146.html

In my own experience, the two seem largely unrelated and a supposed association cannot explain sudden changes.

 

[Firestormm]

Meanwhile, Klimas now attributes autonomic symptoms to "deconditioning" and is into physical rehabilitation?

http://www.mecfsforums.com/index.php/topic,14672.msg146146.html

In my own experience, the two seem largely unrelated and a supposed association cannot explain sudden changes.

I've been reading some of the patient notes from that call, Bio. CFIDS AA have said a full transcript will apparently be available in a couple of weeks. Schwietzer's comments that I read here are supplemented by others on that thread who also made notes during the presentation and at least one blog, here, that also adds further light to what was said.

It doesn't appear to have been as 'controversial' as was first reported. 'Even' Newton is not saying 'don't exercise'. She preferred to talk about 'Graded Activity' considering it more appropriate to the condition; but the point was very similar I think to what I have gleaned from the comments about Klimas and Sol thus far.

Trying to establish one's capabilities on an individual level and then trying to plan what activities are appropriate and building them up slowly are key. And knowing when that build up is proving too much and necessitates a rest and/or revision in the programme. What does still concern me is that when papers are published, and advice afforded to medical professionals generally, this personalisation and establishment of tolerance levels can get overlooked.

There is also the concern that for some patients even Graded Activity is inappropriate. This tailoring of clinical care and the whole 'rehabilitation' remain areas of concern for me. But even when, let's say, Newton's work on the muscle-cells confirms the problems we have in engaging with and then recovering from exercise - it will not remove the clinical desire to help us to exercise appropriately as part of an overall rehabilitation. Neither will it remove the desire from patients to want to 'do more' in an appropriate and personally tailored way.

One area I don't think we've looked into very much is what can happen to the body when it hasn't been exercised for a while - and what exercise achieves in terms of positive benefit at the biological level. Although Simon's thread here did raise these issues I seem to recall at least from one perspective.

It would be useful to read more people's comments from that conference featuring Klimas I think and I'm sure Cort for example will have something to say about it all. Probably deserves it's own thread at some point.

 

[alex3619]

In fit patients with sudden onset a crash in capacity is very fast. Any model wanting to justify deconditioning has to explain this.

Please note though that the claim is that dysautonomia NOT ME is due to deconditioning. I don't know that we can blur the two and still sensibly discuss it. There is then speculation on how much this might explain fatigue etc.

I have very strict exercise limits. Yet when I have a rare partial remission I suddenly can do a lot more, and when it ends I suddenly can do a lot less. Deconditioning might contribute to my issues, but it is most likely not the cause. Since most of my remissions are about six hours, to invoke deconditioning means I gain and lose a lot of fitness in just six hours.

It is also the case that there are subgroups, and not everyone benefits from the same things.

Now even if we throw deconditioning in the trashbin as an explanation, this does not invalidate the idea of sub threshold exercise as a treatment. These are separate concepts. I do think though that we need to run tests to find that threshold, and that something else needs to be found for the severely and very severely affected. I am fairly sure that with proper tests, proper care, and proper monitoring, then subgroups of us will be able to benefit from careful exercise. This however is very intervention intensive, and hence expensive.

I prefer biochemical models. The idea is that if a biochemical change occurs (hormones or other things) then it can suddenly change our metabolism, for better or worse. The changes in muscle pH and how this affects brain circulation could be important in this respect.

I would also want to know if different muscle fibres of different response subgroups stain differently for enterviruses etc. including Coxsackie B3.

This thread should be read alongside the recent published paper, a thread on it is here:
http://forums.phoenixrising.me/index.php?threads/new-article-by-the-newcastle-team.21358/

There are three things that I think are important. When rested our muscles are too alkaline. When active our muscles go excessively acidic. Alkalinity is associated with poor brain blood flow.

Trying to identify the underlying biochemistry may finally unravel the cause of most PEM, OI and brain fog. This is interesting research.

 

[Valentijn]

In fit patients with sudden onset a crash in capacity is very fast. Any model wanting to justify deconditioning has to explain this.

Please note though that the claim is that dysautonomia NOT ME is due to deconditioning. I don't know that we can blur the two and still sensibly discuss it. There is then speculation on how much this might explain fatigue etc.

I have very strict exercise limits. Yet when I have a rare partial remission I suddenly can do a lot more, and when it ends I suddenly can do a lot less. Deconditioning might contribute to my issues, but it is most likely not the cause. Since most of my remissions are about six hours, to invoke deconditioning means I gain and lose a lot of fitness in just six hours.

Agreed ... there is no scientifically supported theory of deconditioning I've ever seen that explains either PEM or sudden remissions where I temporarily went from level 2 functioning to level 6 or 7. Did I need to gradually improve my conditioning? No! The improvement was literally overnight, and the next day stairs and almost a full day of shopping (via bus and walking) were no problem aside from PEM-free mild muscle soreness.

Same thing with onset. Stayed home with the flu for a couple weeks, went back to class, and had PEM symptoms when I got home. And trying to stay at the same level of activity just wasn't possible ... the crashes came easier and easier, and my reductions of activity came after hard-fought battles against those lowering thresholds.

Anyone know if there's any research backing Klimas' claim that deconditioning results in high adrenaline levels?

 

[Firestormm]

Yeah I don't get deconditioning. I can understand that being unable to exercise means that we might suffer as a result of not being active - biologically and mentally.

But I don't think this can be equated to understanding why PEM occurs other than saying over-exercising or inappropriate exercise or an activity management plan that is inappropriate or a programme that is not personally tailored and does not include necessary flexibility - or patients fighting too hard to 'overcome' their condition or being ill-advised: can lead to what patients might infer as a 'relapse'.

Of course when we obtain this diagnosis it may well have been triggered by an infection i.e. viral. A relapse might indeed - often is I would suggest certainly in my case - be tripped by a subsequent and unrelated perhaps infection. I think it is very hard to apply a carte-blanche approach that is relevant to everyone at all times. And I don't think that is what is meant to happen in clinical practice.

What we are witnessing are various attempts at trying to understand the symptoms and that will result in sub-categorisation: even 'fatigue' perhaps. These will not be appropriate for all of us or for all of us at all times. What I hope it might lead to is not only a better understanding but better treatments more appropriately applied.

Like off-label drugs we were discussing on the other thread - GPs and patients would have a selection of treatments and advice to chose from that are most commonly associated with ME. As time goes by and more research is able to link symptoms to treatments - this range will expand and/or be improved/made more relevant.

Whether or not any of this will lead to a single identified cause for all the most common symptoms I don't really know. It's possible I guess and I have ever maintained that if something is discovered for the majority or significant minority it will relate to the immune system.

But. Exercise does carry benefits for the immune system. As do other things of course. All a question of individual relevancy and balance.

 

[Esther12]

Thanks for that Fire.

re deconditioning and autonomic problems: It can also be that certain types of exercise are not appropriate, and certain are. For everyone exercise has costs and benefits, and different forms of exercise will have different costs and benefits. It was always ridiculous to assume that those with CFS could be reassured about the safety of exercise without having any understanding as to the cause of disability, but maybe this sort of autonomic research will be able to help find why some suffer particularly badly from certain types of exercise, but may benefit from others. This is all complicated by the level of quackery that there is in this area: there seems to be an ideological push to exaggerate the benefits of exercise for health (not just for CFS, although we're a good example), and a lot of the claims being made for the benefits of exercise seem based upon poorly done studies. Another complicated and controversial topic.

 

[Rooney]

My memory of the Klimas presentation was that deconditioning was part of the problem, not all the problem. Her theory is not at all simplistic and is flexible per individual. It hit home for me with severe OI, no remissions and slight decline through the years. She said activities of daily living are exercise and should be controlled with a heart monitor. For true exercise, be on the floor with the what is the tiniest of effort to start. Nothing aerobic here.

So, I'm going to try the monitor again. My stairs sends the alarm through the roof.

 

[Enid]

It;s good work/research (having passed out 3 times and with abnormal MRI brain scans) keep going. We need research like this in order to understand the whole picture.

 

[Shell]

I thought Dr Klimas had said that enforced bedrest produced the best outcomes for remission/recovery in ME. Now she seems to be doing an about turn and saying we should have some form of GET. I am confused.

 

[Andrew]

Considering that the ICC says PESE is part of the syndrome, and Klimas was on that panel, I don't see why she is ignoring it. Also, everything I've read by Klimas elsewhere is describing something other than graded exercise. So this is very confusing.

 

[Simon]

View original slides at Vimeo

sound quality is shocking but it's handy to have sound off and see the original slides along with Firstormm's excellent transcript. Nb lecture itself with slides stops after about 23mins, then it's just questions

Great work, on the transciprt, Firestormm, thank you. And I'm particularly looking forward to the results of their studies using metaphysics ("we’re doing plasma-volume with meta-physics"): I think this is the kind of novel approach that the field needs.

 

[SOC]

I suspect we're confused because most of us (me included) haven't heard the Klimas/CDC complete talk yet. There's probably a lot more subtlety than just that we are deconditioned and need to exercise.

My experience with Dr Rey and Connie Sol with regard to activity recommendations may (or may not ) add something to this conversation. They have me wearing an HR monitor to regulate my daily activities so that I don't exceed my AT. My own observation is that keeping a general eye on my HR also lets me know when I'm not doing so well -- my HR is higher than usual for common activities -- and should cut back. I can also tell when I'm doing too much in a day, even if I don't go over my AT, because my HR starts to rise. I don't know if this is true for everyone.

I do have an exercise plan and it's very, very mild. I exercise lying flat for 1 min, then rest for 1 min 5X. Yes, that's a grand total of 5 minutes of exercise. I have not been able to build up because of some uterine issues and surgery, but now that that's past, I can probably build up slowly. You won't see me taking long walks any time soon, though.

The benefit to me of the exercises I was given is that after years of bed and recliner rest, my abdominal muscles are very weak. Strengthening them probably will make it easier for me to do more upright activities as other treatments improve my physical situation. We're not talking weight-lifting, walking, or even sit-ups here. Not for me, anyway.

I'm looking forward to reading the transcript when it comes out. In the meantime, I'm reserving judgement.

FWIW, I was given exercises 1-4 on this page as my "exercise program". http://www.mstrust.org.uk/information/exercises/index_lying.jsp
Not exactly 'Rocky'.