Firestormm - thanks for your monumental effort to create the transcript. It must've been exhausting.
I share some of
Research 1st scepticism of Dr Newton's work:
As you've 'tagged' me jimells, I thought I would reply. It did take some considerable time and effort to transcribe and I appreciate your recognition of that. I am not 'sold' on Newton - I don't think we need to be. Similarly I don't think it's helpful to have a preconception that any research coming from Newton or her colleague at Newcastle - will answer all the questions for everybody.
I don't think this is realistic in regard to any research. I also don't think it helpful to have a preconception as to what we might think our condition is or is not. But that's just me trying (and probably failing) to remain objective.
Julia Newton is a specialist in Syncopy (feinting and/or black-outs) and Ageing. It is her research that has helped shine a light on the significant proportion of patients with our condition who suffer from Orthostatic Intolerance/Autonomic Dysfunction/Low blood pressure/POTS. A proportion that outshines those with other chronic conditions.
In slide 8 she showed that nearly 90% of patients in her study with CFS/ME had symptoms of OI when standing up, and this was significantly more than in other diseases used as comparisons in several of her studies such as Fatty Liver Disease 56% and Primary Biliary Cirrhosis 69%.
She also, in slide 7, indicated how CFS/ME compared to 'Controls, NAFLD, PBC, PSC, OLT, VVS, ITP and Sjorgen’s' all of which are regarded similarly as 'fatigue-associated' conditions. This also demonstrated how highly and similarly CFS/ME patients reported symptoms associated with OI.
For a long time now I have been hearing from people who had great difficulty getting those symptoms attributed to POTS recognised as a legitimate complaint - let alone being tested or indeed treated for it. This area of her research (and the grant from the MRC) will help these people and it will lead (hopefully) to more people (and doctors) who did not realise that this issue could be causing their difficulties, to receive acknowledgement and treatment.
Newton is not a neurologist. However, Newton's research has suggested to her that for those people who do lack this 'head of steam' i.e. low blood pressure, when compared to other chronic conditions whose other symptoms also feature fatigue - it could if treated perhaps relieve them of this additional impairment.
Slide 4 did feature Multiple Sclerosis and this fatigue association as well as a paper in the Journal of Neurology:
In a range of diseases characterised by fatigue (MS and heart failure) – strong associations between fatigue and autonomic dysfunction.
o Flackenecker et al. Neurology 2003,
o Naschitz et al. Seminars in arthritis and rheumatism 2002,
o Streeten et al. Am J Med Sci 2000,
o Stewart Ped Res 2000,
o Peckerman et al. Psychosomatic medicine 2003.
Fatigue is a symptom in PAF & MSA which are characterised by abnormalities of blood pressure control
o Mathias et al. Journal of Neurology 1999.
So, poor 'head of steam' = orthostatic intolerance = cognitive problems = possible link to fatigue. I mean it seems to me (a layman) that if my body is not able (for whatever reason - the heart?) to generate sufficient blood pressure to see blood reach all my organs as quickly as I need it to - then my organs (my body) is going to be 'starved' of esp. oxygen.
This isn't especially new either. She pointed to an original article/paper appearing in the Lancet Rowe et al; Is neurally mediated hypotension an unrecognised cause of chronic fatigue? Lancet. 345(8950):623-4, 1995 It just hasn't been well recognised.
If I lack oxygen I am going to feel fatigued, to have problems concentrating, to experience recall issues, and even forget stuff and might describe all of this as 'brain fog'. One silly example I might use is this:
Sat in a sealed room with a real fire. The fire takes the oxygen out of the air I breathe. The longer I am there the sleepier I feel. I am in effect oxygen-starved. If I was to conduct cognitive challenges then the longer I was there the poorer the results would be. Eventually, if the fire kept being replenished, I would die.
Quite what effect, if any, this lack of oxygen has on the muscles and on the brain itself - long-term - I don't know. But could it account for 'inflammation'? It might be interesting to ask Julia for her thoughts on this. What causes the low blood pressure in the first place? I don't know either but she cites and talks about cardiac function - and several papers are listed below that I should probably read.
The other study I thought of particular fascination, was what she had completed on muscle and exercise function. The exercise inside an MRI and then taking muscle cells and 'exercising' them in a laboratory 'gym'. I mean that is so cool and the first time I have ever heard this happen.
Having been around for a while, I know that people - including Dr Charles Shepherd of the ME Association - have endured muscle biopsies. Professor Behan (now Patron of the ME Association) has taken muscle biopsies from patients with ME in the past I understand.
What hasn't happened previously to my knowledge, is an explicit acknowledgement from 'the establishment' in the way that the MRC has done that this line of research - in the way it has been done and is proposed by Julia - is well worth following and funding.
If a drug can one day be developed which will relieve me of not only the autonomic dysfunction, but the fatigue, and the constant pain in my muscles exacerbated by exercise - I will be chuffed to bits.
It might not work out like that. It might not solve all my problems. But it is one of the best and most hopeful presentations I have ever listened to and a research direction that I think holds promise for a lot of people. It will also serve (has served) to gain greater recognition for our condition and link it to and place it above the symptoms experienced by other chronic illnesses. And that can't be bad news either.
I also look forward to hearing from her colleague, Dr Wan Ng and his immune system work. It may complement Julia's work or it might conflict or it might provide some answers for different people in the 'pot'. Whatever the outcome of it I hope some 'fingerprint' can be found. What the effects long-term of 'fatigue' and of the symptoms we attribute to ME are on the body, I don't think anyone has ever looked into and perhaps someone should; but if a biomarker of some description is forthcoming in relation to the immune system it would further help quantify matters.
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
I said earlier I'd list all the papers Julia cited in her presentation. She said at the beginning there were over 200 papers relating to CFS/ME and problems with the vascular or autonomic nervous system. I will come back and add links to the actual papers listed below. Unhelpfully she didn't cite them in full so I'll need to dig a bit I expect and I'm knackered now:
Slide 3:
Rowe et al; Is neurally mediated hypotension an unrecognised cause of chronic fatigue? Lancet. 345(8950):623-4, 1995
Slide 4:
Flackenecker et al. Neurology 2003,
Naschitz et al. Seminars in arthritis and rheumatism 2002,
Streeten et al. Am J Med Sci 2000,
Stewart Ped Res 2000,
Peckerman et al. Psychosomatic medicine 2003.
Mathias et al. Journal of Neurology 1999
Slide 9:
Newton et al., QJM 2007
Slide 11:
Newton et al., Psychosom Med 2009
Newton et al., CAR 2009
Slide 12:
Newton et al., Liver Int 2006
Newton et al., EJGH 2006
Newton et al., Hepatology 2006
Slide 14:
Newton et al., CAR 2009
Slide 18:
Jones and Newton JIM, 2009
Slide 21:
Hollingsworth et al., EJCI 2010 & JIM 2011
As I said I'll complete the links to the actual papers later today perhaps though if anyone else wants to lend a hand I'd appreciate it. Thanks