Science at the UK CMRC Conference, 1-2 Sept 2014

[Sasha]

Not that I recall.

Ah well - maybe next year.

I realise that part of the aim of this conference was capacity-building and that certain areas (fatigue, pain) were focused on to bring in new expertise from other diseases and that the intention wasn't necessarily to represent the full range of endeavour, but were there particular areas that you'd like to see included or emphasised in the next conference?

 

[MeSci]

In a joint a macrophage can turn into a 'synovial type A cell' or a 'tingible body macrophage' or a 'T cell zone macrophage' or a 'haemosiderin laden macrophage'.

I thought that 'tingible body macrophage' must be a typo, but looked it up and found that it is "A term of art for an ordinary macrophage in a reactive germinal center. Tingible body macrophages are characterised by sparkling intracellular material"!

Source: http://medical-dictionary.thefreedictionary.com/Tingible+Body+Macrophage

It sounds pretty!

 

[MeSci]

@Jonathan Edwards - maybe you missed this post of mine in which I asked:

Some of us have noted that our PEM is like a hangover. I understand that hangover symptoms are mainly due to dehydration and loss of electrolytes.

I suffer from solute diuresis after exertion - haven't yet analysed when it starts, but suspect that it is the day before my PEM appears. My PEM usually appears about 48 hours after the exertion, but at better times it has taken up to a week and been extremely mild - almost imperceptible. At least one other contributor, however, has said that a longer delay is associated with worse PEM for them.

So, what could be causing solute diuresis after exertion? (I had been thinking along the lines of inflammatory cytokines, but have read your reservations about this.) And could solute diuresis/dehydration/electrolyte deficiency help to solve the mystery of the delay? That it takes a while for something to cause the diuresis, and then further delay before the dehydration and electrolyte loss reach a level sufficient to cause symptoms? (Consistent with a solute diuresis cause of PEM is the fact that several people report great improvement - even remission - from being given IV saline.)

There is a thread on PEM being like hangovers here.

Admittedly there are PEM symptoms which I don't think are seen in hangovers, notably swollen/tender lymph nodes. So could your suggested lymphocyte/macrophage interaction/macrophage influx into muscle fit into the solute diuresis connection?

 

[aimossy]

I would love to hear more about the gut science - alas it is not to be!
I would have liked to hear more from Dr Lipkin about his thoughts on the gut microbiome work and hope he talked about it - if not in the formal manner but at least with other researchers. Maybe there was an embargo.

My interest is mainly because I am very keen on gut research and so fascinated with the gut brain axis. Basically because I care about mine, as I am the one who has to put up with my gut and brain symptoms which feel so interconnected it's mind blowing. Often I wished you could have a doctor have your own body for a week till it made them loopy with discomfort, our symptoms sound unbelievable to our own ears, so it is frustrating if you try and explain them.

But I am really so pleased that this conference enabled researchers to chin wag together and pass on to each other all their info and make connections with each other. @Jonathan Edwards you were hoping to get to speak to a few, did that happen and was it useful for you?

 

[lansbergen]

Some of us have noted that our PEM is like a hangover

I do not know about PEM but when I forgot to take the immunemodulator I got a hangover the next day. I have not forgotten for a long time now so I do not know it is still the case and I am not going to test it. .

 

[Jonathan Edwards]

@Jonathan Edwards - maybe you missed this post of mine in which I asked:
So, what could be causing solute diuresis after exertion?

I don't think I can give an intelligent answer to that one - maybe that is why I 'missed' it.

 

[Jonathan Edwards]

But I am really so pleased that this conference enabled researchers to chin wag together and pass on to each other all their info and make connections with each other. @Jonathan Edwards you were hoping to get to speak to a few, did that happen and was it useful for you?

I think I spoke to almost everyone. It was very well structured for that.

 

[Marco]

Tissue microstructural changes in brains could easily go unnoticed.

Not to dismiss this possibility that I feel is actually more than likely but I was thinking more in terms of peripheral tissue damage. To refer back to the fibro example 50% approx were found to have peripheral neuropathy and the interpretation taken to date seems to be that it's 'misdiagnosis'. But with any such test (skin punch biopsy) there has to be a cut-off point between yes and no. Could the rest be 'subclinical' as far as that test is concerned but the peripheral damage is still driving the central sensitisation? Lots of folks here report symptoms consistent with peripheral (and autonomic) neuropathy.

Sorry to skew the discussion off into a whole other can of worms but its that sort of condition.

 

[Jonathan Edwards]

I guess all sorts of different things may be going on but unmeasurables in places that we can study rather easily are to my mind less plausible than ones in places we cannot get at. In all this stuff I need to think of specific pathways. 'Neuropathy' is too vague for me. Is there terminal branch drop out or axonal drop out or demyelination or what? And I find it difficult to relate nerve fibre drop out to ME symptoms, which fluctuate and depend on exertion etc. Neuropathic pain as I understand it is just there all the time. My radiculopathic pains certainly are.

I think you are right this may be a can of worms. I find it quite hard to believe that anybody can diagnose 'fibromyalgia' reliably enough to pick out a group of people with the same pathology to be honest. Whenever I have come across physicians talking about fibromyalgia my impression is that they are talking horse manure.

 

[Marco]

I think you are right this may be a can of worms. I find it quite hard to believe that anybody can diagnose 'fibromyalgia' reliably enough to pick out a group of people with the same pathology to be honest. Whenever I have come across physicians talking about fibromyalgia my impression is that they are talking horse manure.

The story of my diagnosis after many years was that my GP suggested fibromyalgia. I responded that I didn't have the 'classic' tender points (now highly disputed as even slightly relevant). OK then - how about M.E? - Sounds OK.

Next appointment I asked how we might start to treat this 'ME' and he stated that I can't have ME - its chronic fatigue syndrome. Both 'diagnoses' still print out on my computerised NHS record.

Its a mess!

 

[Simon]

Sorry, I'm laughably behind with this thread

Andrew Lloyd: Acute infection and post infective fatigue as a model for CFS
...
His final conclusion was that persistent fatigue was not due to persistence of the organism or indeed persistence of a systemic host inflammatory response (as judged by blood cytokines) so must be due to some resetting of a regulatory mechanism within the central nervous system. He did not enlarge but microglia might have been in his mind.

I think they were, judging by this 2008 paper of his on the Dubbo study:
Cytokine Polymorphisms Have a Synergistic Effect on Severity of the Acute Sickness Response to Infection.

Animal studies indicate that peripheral cytokines induce de novo synthesis of cytokines from resident microglia and astrocytes [43, 44]. The mechanisms for translation of these cytokine signals into altered neural transmissions remain unclear. of interest to the association we observed between severity of the acute sickness response and the duration of illness manifestations is the growing awareness of a prevalent microglial response to a range of infectious and inflammatory stimuli via Toll-like receptors (reviewed in [45]) and the recognition that a single exposure to LPS-induced TNF-α may trigger microglial activation that is sustained for 10 months in the absence of systemic inflammation [46]. Accordingly, we suspect that in individuals with a prolonged postinfective illness, a prominent cytokine response in the acute phase causes sensitization in these CNS pathways, which leads to sustained neurobehavioral phenomena that manifest with ongoing symptoms in the absence of persistent peripheral cytokine production.

This ties in with the view you described from the conference that the problem is tied to persistent activation rather than persistent infection/

 

[Kati]

Whenever I have come across physicians talking about fibromyalgia my impression is that they are talking horse manure.

Yep. And you can imagine that no physicians with fibromyalgia dare coming out of the closet. And rare are physicians admitting they have ME

It speaks volume to me.

 

[lansbergen]

. Neuropathic pain as I understand it is just there all the time. My radiculopathic pains certainly are.

That maybe but mine fluctates. Now I have so much improved .I sometimes wake up in the morning painfree. As long as I keep laying it stays away but even only sitting on a chair behind the computer brings it back.

 

[lansbergen]

@Jonathan Edwards

Does this help? At a certain point of my improvement my memories came back. Not all at once but bit by bit. It happened in such a short time span that I concluded there could not be much permanent damage. It took a while to store the informatie at the right places .

 

[Jonathan Edwards]

That maybe but mine fluctates. Now I have so much improved .I sometimes wake up in the morning painfree. As long as I keep laying it stays away but even only sitting on a chair behind the computer brings it back.

But is that associated with a neuropathy, i.e. a structural change in nerves as indicate by absent reflexes, loss of pinprick or vibration sense or electrophysiology or biopsy? I was using 'neuropathic' in the technical sense of resulting from a neuropathy. Compression neuropathy or radiculopathy, such as sciatica or carpal tunnel syndrome will certainly fluctuate with posture but the suggestion in the 'fibromyalgia' studies is of a diffuse neuropathy as far as I can see. Pain from diffuse neuropathy is usually in the feet and hands and more or less unchanging in my clinical experience.

 

[NK17]

Yep. And you can imagine that no physicians with fibromyalgia dare coming out of the closet. And rare are physicians admitting they have ME

It speaks volume to me.

Well my old geezer of a rheumatologist has admitted that he suffers from fibromyalgia @Kati.
His specialty is scleroderma but he sees patients with many different CTDiseases as well as fibromyalgia and the ones like me with ME.
At the last visit I told him about the young neurologist, familiar with Dr. Anne Louise Oaklander @ Mass General, who ordered a punch skin biopsy to verify if my fibromyalgia was due to small fiber neuropathy.
My rheumatologist was surprised about the skin biopsy, he had never heard about it in the setting of fibromyalgia diagnosis, or shall we call it misdiagnosis?!
Too bad the biopsy came back negative. I'm still stuck with a fibromyalgia dx from the rheumy.
I honestly think that my fibromyalgia is just the myalgic part of ME and that is the reason why, so far, no treatment has been able to abate the multi-natured pain.

 

[NK17]

But is that associated with a neuropathy, i.e. a structural change in nerves as indicate by absent reflexes, loss of pinprick or vibration sense or electrophysiology or biopsy? I was using 'neuropathic' in the technical sense of resulting from a neuropathy. Compression neuropathy or radiculopathy, such as sciatica or carpal tunnel syndrome will certainly fluctuate with posture but the suggestion in the 'fibromyalgia' studies is of a diffuse neuropathy as far as I can see. Pain from diffuse neuropathy is usually in the feet and hands and more or less unchanging in my clinical experience.

I've had a couple of EMGs as well as the punch skin biopsy @Jonathan Edwards, all negative.
I suffer from CTS, was first diagnosed during pregnancy, when I also had the typical lupus rash (I'm quite photosensitive and since I don't sweat anymore, I can't stay in the sun, even if I wanted to absorb my daily Vit D dose).
Recently the CTS came back with a vengeance because it just feels like the 'cherry' on top of all the other aches and pains.
Well before being diagnosed by Dr. Kogelnik I've been experiencing what you I've just described as diffuse neuropathic pain. I've been keeping a diary and frequently I've complained about feet and hands pain (burning, prickling, numbness etc.).
As a matter of fact I'm experiencing it right now while posting on PR while laying down.
This neuropathic pain can be pulled apart from muscular pain and joint pain.
All of the above are also more frequently coupled with brain and spinal cord pain, what I can describe like ongoing brain inflammation.

 

[lansbergen]

But is that associated with a neuropathy, i.e. a structural change in nerves as indicate by absent reflexes, loss of pinprick or vibration sense or electrophysiology or biopsy? I was using 'neuropathic' in the technical sense of resulting from a neuropathy. Compression neuropathy or radiculopathy, such as sciatica or carpal tunnel syndrome will certainly fluctuate with posture but the suggestion in the 'fibromyalgia' studies is of a diffuse neuropathy as far as I can see. Pain from diffuse neuropathy is usually in the feet and hands and more or less unchanging in my clinical experience.

I doubt it is still at the root of the sciatica nerve but it is still in the pelvic area. When I put Benzydaminehydrochloride cream at the inflammed spot the pain in leg lessens and the cramps stop. When I walk many times my foot comes in late and I stumble. When I was still worse my legs suddenly would not carry my weight and I fell.

Higher up, my pupil reflex does not work well. I noticed the pupilreflex problem in the animals too

This disease has such weird symptoms.

 

[NK17]

I doubt it is still at the root of the sciatica nerve but it is still in the pelvic area. When I put Benzydaminehydrochloride cream at the inflammed spot the pain in leg lessens and the cramps stop. When I walk many times my foot comes in late and I stumble. When I was still worse my legs suddenly would not carry my weight and I fell.

Higher up, my pupil reflex does not work well. I noticed the pupilreflex problem in the animals too

This disease has such weird symptoms.

Indeed we really experience weird neurologic symptoms which seem to come and go, sometime, with no rhyme and no reason.
I wish I had been seen by a doctor when I had a long episode of Adie's pupils, or at least took a picture.
Both my pupils were dilated and I did not take any drug that could have possibly caused that.
Doctors can only trust what I tell them and honestly if I was one healthy doctor, I would find it difficult to believe that so many symptoms can exist in one single human body!
We definitely need more medical doctors and students affected by ME, not that I wish this to anyone .

 

[Kati]

I've had a couple of EMGs as well as the punch skin biopsy @Jonathan Edwards, all negative.
I suffer from CTS, was first diagnosed during pregnancy, when I also had the typical lupus rash (I'm quite photosensitive and since I don't sweat anymore, I can't stay in the sun, even if I wanted to absorb my daily Vit D dose).
Recently the CTS came back with a vengeance because it just feels like the 'cherry' on top of all the other aches and pains.
Well before being diagnosed by Dr. Kogelnik I've been experiencing what you I've just described as diffuse neuropathic pain. I've been keeping a diary and frequently I've complained about feet and hands pain (burning, prickling, numbness etc.).
As a matter of fact I'm experiencing it right now while posting on PR while laying down.
This neuropathic pain can be pulled apart from muscular pain and joint pain.
All of the above are also more frequently coupled with brain and spinal cord pain, what I can describe like ongoing brain inflammation.

I can relate well to the feeling inflamed brain and spinal cord. Many days it feels to me like I've been hit in the back of the head by a baseball bat. And I wake up pretty much every day with pain down my spine. It is not muscular.

My GP has pretty much tuned my symptoms out and despite elevated ESR and CRP, nothing will make her believe me when i say I have lots of inflammation in my brain and spine.

The prickly feeling in my feet I don't mention because it's buzzing all the time, especially when i am laying down like now. It's a bit like radio on the AM dial, in between stations. (Oh wait, I can't say that, someone will call the psychs on me)