What differentiates ME/CFS from known primary mitochondrial diseases; could mitochondrial disease cause PEM?

> muscle damage and progressive nature. It’s not the same condition clearly, but there can be some symptom overlap sometimes, although there are also some differences & specific symptoms doctors look for in mitochondrial disease such as the organ involvement.

i'm confused here because muscle damage is rarely tested for and m.e. is very often progressive course.

also what organs? many pwme i believe have problems in organs that get worse. all sorts of eye problems and more.

> that I am annoying people, or clogging up an ME forum with posts about another condition!

i'd love more "annoying" [not] and "clogging" [not] posts like that. informative and raises key diagnostic questions.

in light of your post, i think i do not fully understand how we can confidently diagnose m.e. without a lot of testing.

your mito description seems like it could be more plausibly confusible with some cases of meicc m.e. than depression or thyroid.

even with testing, not really sure about some things. e.g. sle is variable in presentation. yet i was told my clinical picture doesn't match sle. which parts? my anti-ds dna is above normal and that is supposedly in general a highly specific test for sle. do i have both?

> PS I think there’s a list of conditions from the ME association for differential diagnosis, but pretty sure more than 50% of the conditions listed are not routinely tested for, before giving a diagnosis of CFS on the NHS.

what does one do to diagnose post-polio vs. m.e. assuming p-p resembles or produces m.e.?

 

I had muscle testing, mostly electrical tests, and a few blood tests related to muscle, but no biopsy, as part of a research study I volunteered for, not regular testing. I had massively elevated enzymes suggesting muscle damage yet no clear damage could be found.

 

This is so interesting. For me this really gets to the heart of a lot of my confusion about what I "have" and what ME is (or isn't). I'm sure I'm not the first person to finding themself grappling with this puzzle. Also I have had no medical training so the next part might just be basic undergrad medicine!
I keep being thrown back & forth on the question of whether ME is a "positive" diagnosis (e.g the presence of something measurable - a virus/pathogen/particular system(s) or process(es) not working properly, which are causing a particular set of symptoms)
or a "negative" diagnosis - e.g a set of symptoms (not universally agreed upon but with some level of consensus e.g presence of at least 1 of PEM, POTS, non-PEM fatigue, brain fog/concentration issues, + others) which can't be explained by any of [insert list of things to rule out as discussed in previous posts].

I'm particularly interested @Jonathan Edwards in why "it is important not to think that everyone with ME needs to get tested specifically for mitochondrial disease." - if the symptoms are so similar, and if as seems to be the case in practice - ME is a diagnosis that can only be arrived at once other things have been ruled out, wouldn't it be logical for mitochondrial disease to be one of those things to rule out?

I think I understand from what you've been saying so far that the reason it isn't important is because ME is actually something different, but then I get confused again because I thought one of the many problems is that we don't know what ME is? I appreciate this is all getting a bit circular but it seems to highlight the bizarre circularity of some of the conventions around ME... There must be lots of people (like me) who essentially have been left with a diagnosis of ME because some other things have been ruled out, but if for every person that list of other things that have been ruled out is a different list, then ME just means 'set of symptoms not explained by some possible causes, but potentially explained by many other possible causes that haven't been checked for...'

In which case to say that people with ME don't need to be checked for mito disease because they have ME, when we can only know if they have ME once we know that they don't have mito disease.. feels like a circle my brain can't square!

This has become much more rambly than I anticipated... I hope it makes sense...

 

Thanks for finding this @lunarainbows - another basic question from me now - so in theory is the idea that everything on that list needs to be ruled out in order to make an ME diagnosis?

 

As I understand it the symptoms are not similar.

I think patients get into thinking that if two diseases include headache or shortness of breath then that means they are likely to be similar. Medical diagnosis goes way beyond listing symptoms.

It is a bit like saying that two problems that cause an outboard motor not to start will be similar. But an engineer wants to know whether it always will not start, whether the problem has come on suddenly, whether the engine has been making an unusual noise and after finding all that out the problem is likely to look completely different in each case.

From my understanding, the time relation between symptoms of ME and exertion is quite different from the immediate relation that would apply if ATP had run out. I also know lots of people with ME now and none of them show any of the sort of outward signs that I have seen in people with metabolic failure (most often secondary to renal failure or heart failure). Nor do they show the pattern of outward signs of people with weakness from muscular dystrophies. They are as different as chalk and cheese.

And the fact that people with ME may show some features a bit like mitochondrial disease and some people with mitochondrial disease show some features a bit like ME. The motor engineer is used to the fact that not always the history of the problem is typical. He picks out a pattern that makes him think the likely issue is with dirty fuel or the plug or the carburettor.

Part of the problem is the medical care is now functioning so much below what it could do in many Western countries at least - for reasons of politics, Covid, bureaucracy, whatever - that diagnoses may well get missed. But if someone skilled at taking a medical history and familiar with both conditions were asked to discriminate likely ME or mitochondrial disease cases I don't think they are likely to have much difficulty.

 

I 100% agree with your comment. There was another thread somewhere where I noted that the issue is when people talk about 'ME/CFS' we don't even know which 'cohort/context' we are using. As an approx of what I mean by that (and it isn't about definitions):

1. Those who have ME/CFS as per scientific research. As of more recent and using certain criteria papers these will all have PEM. Most likely to be milder due to participation required. Probably less likely to have comorbidities due to methodology reasons.
2. Those who have ME/CFS as per BPS research. People with fatigue. Most likely to be milder if they have ME/CFS to begin with, and anyone with PEM filtered out by dropping out of treatments and follow-up that cannot be completed if you have it.
3. Those who have ME/CFS as per diagnosis by GP, clinic or whatever. This is a dumping pot, and from some people's experiences was really encouraged as almost a policy push for bucket diagnosis of those with illnesses not on a red flag list. From my experience and many others, pretty much all have PEM but very few had much investigated before, during and definitely after any diagnosis. The guidelines told them not to. You could in fact define us as the group mostly 'refused access to tests' certainly since 2007, due to the clear instructions in the guidelines inferring this would 'only encourage hypochondria'.

So contrary to what BPS would have everyone else think, it is often very ill people who have PEM including probably a high proportion of other comorbidities and misdiagnoses for undiagnosed biomedical illnesses. It could be that the ME/CFS is a 'preceder', or just plain missed diagnosis, or that some of these conditions work in such ways that in some certain symptoms come before others. They've been sat rotting on GPs lists in the main with noone interested in what probably is a big chunk of medicine - not just 'a condition'.

Luna, Peter, and many of us are talking about group 3 as much as group 1 - noting even what is meant by that could be an umbrella diagnosis. SO there may well be different types for different reasons?

It is highly relevant because as Luna notes at points this will include people with other conditions who if there were diagnostic centres covering all the related suspects probably would expand knowledge for all these conditions. Others are noting there seem to be overlaps and spectra for certain other conditions (some of which are diagnosed by symptoms/history, other by biomarker/underlying mechanism).

And as Peter notes we have a (to the layperson) strange system where misdiagnosed who turn out to have something else (40% I've heard) are not kept track of (!) or fed back into the refining of either the ME/CFS process nor the other condition they turned out to have.

And Luna and others in other thread's notes about other conditions causing PEM is relevant twofold:

• a lot of ME/CFS patients note that PEM/energy limiting aspect is the primary symptom in as far as it feeling like whatever is causing that is driving the 'condition'. Given the above bucket/spectra/scale issue, it seems feasible insight to rule in or out.
• if we mapped more intricate descriptions of PEM vs the etiology/findings and found the same effects in people where it isn't down to mitochondria etc. that's pretty insightful in itself?

 

Thanks for clarifying - so the process of diagnosis always involves "ruling out" (or I suppose, not ruling in) a number of things without testing for them, because the medic's training & knowledge & experience allow them to exclude a certain number of things.

To (inelegantly) continue with your outboard motor analogy - it seems like Mitochondrial Disease and ME are different categories of thing at the moment (in terms of general consensus and scientific understanding) - is that fair to say? (Genuine question).
As in Mitochondrial Disease is, for example, [faulty spark plug], where ME is [motor won't start].

Are there many of those around? Who are they and how can we get in touch with them?

 

Thanks for this @bobbler !

 

And that is the common ground we are all speaking on.

Who is this ever likely to be? ME/CFS clinics in the main don't even have doctors, just allied staff train predominantly in 'managing CFS' and not enabled to look for or suggest alternates such as these. GPs have for many years just been pathwaying off those with 'approx something' into the CFS pot, with varying degrees of patient speaking/giving history, tests.

It is certainly a big issue for those already diagnosed. Once there the old guidelines suggested they were not to be investigated. Other labels and notes can influence how the above things get 'primed' e.g. GP notes can influence whether these things are interpreted by future people (things like muscle wastage get written off as deconditioning and so on, even if patient says they've been doing stuff so that's not possible).

It sounds like an exaggerating statement to make but I think for the last decade or more ME/CFS 'pot' of patients are the 'uninvestigateds'. There will be some great GPs, there are many patients who feel it is too unsafe to go near medical care. My guess is that what would be even categorised as 'good' comes nowhere near any of this, or any proper history, just check for red flags, 'shuffle you out of the door at 5mins' appts, bung on pathway that is open.

A massive step forward would just be diagnostic centres with fresh, unconflicted pairs of eyes/ears (not reading old conflicted notes) that are enabled, qualified and prepared to make whichever diagnosis is correct at a triage level. I doubt either GPs or most of the same old clinic staff are that, so wonder how that can be remedied to cover things along the lines of this?

 

Yes one is a concept based on an idea of what causes the problem the other is a concept based on a problem needing a cause. Quite different categories. Medicine commonly pigeonholes people into both sorts of categories and often it works quite well. However, it also quite often leads to misunderstanding.

For instance is 'osteoarthritis' a cause of a problem or a problem looking for a cause? Nobody is very clear on that.

These days I do not know but physicians familiar with mitochondrial disease are not that common. They can be found in major university centre neurology departments most often but they may be in clinical genetics or rheumatology or other specialities.

More common are physicians familiar with ME/CFS who has a working understanding of what might suggest mitochondrial disease. They may be in infectious diseases, neurology, rheumatology or just general internal medicine with a special interest.

 

Michael Hanna is very knowledgeable about mitochondrial disease affecting muscle power. He is at the National Hospital Queen Square.

 

As indicated in my replies above.

In the UK we just need a functioning medical care system, full stop. I realise that PWME have had a raw deal but the reality is that the system has collapsed for everything now. Education is going backwards. The whole thing is a disaster because health care professions are no longer seen as good careers to go in to by the intelligent people needed. All the bright kids go in to finance if they can. The health system has been starved of money to the extent that it does not work at all.

 

Sorry Joseph - just re-read it and hope that didn't come across wrong. I was trying to say I agree with you, but also struggling with the 'keeping track of all the rubiks cube bits'. Still not sure I've got there (!?)

Anyway, the use of names was to help me try and organise/remember my thoughts together when writing (as they layered on top of each other, it's all a bit complex and abstract to try and put 'bits' together for me without 'showing my working' by writing it down as a logic puzzle format) - not patronise you/anyone else, just in case it came across that way.

 

Oh - it didn't at all come across as patronising or anything like that. My post was pretty knotty! all good!

 

Agree. Same here. The arms are the most obvious, you just get so used to adjusting how you do things when you are less severe that you don't think to talk about it e.g. never been able to use hair straighteners even when they were what everyone did, or long blow-dry type things where arms would need to keep being raised.

Even when moderate a short walk to shop, carrying a pretty light carrier bag back meant that when I lifted drink to mouth I could not get my arm there,embarrassingly shaking on attempt to do so in front of some colleagues. Yet my arms whilst not bulky at all, would have looked athletic.

This now happens at not a lot these days, and means hours of having to have a pillow stuffed under them because they cannot even support themselves. Drinks must be via straw propped up to chin by cushions at that point.

Any muscle will do this if I use it for too long/longer than it wants - give away is it sort of often does a couple of sharp twitchy jerks at it's 'done' point often. And I can talk myself to collapse if I push through and keep going when I've had to lie flat - you wouldn't think you could collapse when you were already flat and not exerting in any other way.

 

@Jonathan Edwards the problem is you keep saying things that are either incorrect or inaccurate. On a science forum.

First, you said people who have ATP problems don’t feel unwell like ME and they just have difficulty lifting an arm or a leg, (and therefore ATP problems don’t really make sense in ME). But everything I had read (including from scientific papers), & actually experienced myself, said the opposite. It’s not just about being unable to lift an arm or a leg. So I said, but actually, that’s not true, people who have ATP problems do have other symptoms, including excessive fatigue, and feel unwell. So it doesn’t make sense to disregard mitochondrial problems in ME on that basis.

I quoted a website from the NIH that lists several symptoms of mito such as breathlessness, nausea, headache, vomiting, exercise intolerance, muscle weakness & cramping. Are you saying the NIH is mistaken about all these symptoms? I then posted research from Newcastle that mito disease patients do feel unwell with significant fatigue. Even fatigue alone could make someone feel very unwell, but these patients often don’t just have fatigue alone.

I did a quick search & found this on the first search: clinical manifestations of mitochondrial disease. https://bcmj.org/articles/mitochondrial-disease-clinical-manifestations-overview

They discuss several case studies & types of symptoms, this is one:

“Exertional myalgia is a common presenting symptom of mitochondrial disease, especially in adults.
A 40-year-old man presented with exertional myalgias dating back to the age of 14. He experienced fatigue with even minor activities such as walking up a flight of stairs, holding a clipboard, and filling a coffee pot with water.

Clinical history revealed type 2 diabetes and progressive dysphagia. A muscle biopsy done at the time of a Heller esophagomyotomy for the dysphagia (caused by a hypertensive lower esophageal sphincter) revealed subsarcolemmal accumulation of mitochondria and cytochrome oxidase negative muscle fibres, confirming the diagnosis of mitochondrial myopathy.”

Would not “fatigue after minor activities” and pain after exertion, make someone feel unwell?

I could post other papers about many other symptoms, including pain, exercise intolerance, breathlessness & fatigue after exertion. There are case studies of people clinically diagnosed with mitochondrial diseases, from the Lily Foundation, where their seizures, headaches & myoclonic jerks were some of the most debilitating symptoms. These symptoms all make people feel terribly unwell.

The lily foundation, the main charity in the U.K, is sponsoring this study:https://www.thelilyfoundation.org.uk/lily-research/research-funded-date/

“Development of Assessment Guidelines for Balance Disturbances in Mitochondrial Disease

Balance disturbance, including dizziness and unsteadiness, is common in people with mitochondrial disease. The study will support the development of assessment guidelines that help understand the cause of balance disturbance, which will allow for earlier identification and improved management of these disabling symptoms. This will benefit patients by helping to reduce falls, improving safety and enhancing quality of life through access to targeted physiotherapy.”

Again, another symptom - dizziness: this can make someone feel unwell.

Are all these papers and case studies wrong too?


You then did not want to believe people with ATP problems have specific types of exercise intolerance like PEM. (Or “crashes”). Your answer to that wasn’t scientific, it was actually to dismiss it immediately: “I strongly believe that there are lots of diagnoses going on that should be questioned”, & “you should be careful of those in Facebook groups… they may have ME”.

It may be anecdotal evidence and lived experience. But let’s not forget that for PwME too - PEM and pretty much all of their other symptoms beside fatigue, including PEM, are also anecdotal evidence and lived experience too. Yet it is believed, to the extent that it has now ended up in the NICE guidelines. The surveys used for those guidelines were actually recruited through via online means as well.

Why do we take at face value, PwME on this forum & elsewhere, when they report a diagnosis, symptoms, PEM & deterioration, and surveys saying exercise made people feel more ill, but not people with other illnesses, when they report symptoms? Is there a reason for the double standards here?

Lets also remember PEM (and finding out if it’s different when it starts immediately / a few hours later, compared to when it starts a few days later) hasn’t even been studied in depth, since it’s only relatively recently that PwME started talking about PEM. People with mitochondrial disease can report crashes, can report feeling very fatigued and tired after activity, and sometimes a slow recovery from that as well.

It is also untrue for you to say that there is “lots of diagnoses going on”, as it is extremely difficult in reality to get diagnosed.

If someone is not specifically researching the symptoms that people with mitochondrial disease live with, they may not know the full range of symptoms. But doctors, or others who work with directly such patients or research this, will.

And a doctor who works with such conditions, said mitochondrial disease can present with an ME like picture.

I think I’ve made my point on this now so won’t keep discussing it. But I think that 1) there’s some double standards here on this forum, if you want to accept PwME’s word about their symptoms but not others (including what doctors who work with the condition say, or have written in case studies such as the ones I’ve posted above) 2) it is untrue that mitochondrial disease does not produce symptoms that make people feel unwell - sometimes in a similar picture to ME.

 

Yes but in practice no one gets most of these conditions ruled out.

In an ideal world patients should be tested for at least a proportion of them. If it was up to me, I’d say some/most of endocrinological, GI, cardiovascular, neurological & rheumatological - depending on symptoms. The problem is that quite a lot of symptoms (except PEM) that PwME experience are non specific. The endocrinologist I saw earlier on, felt that some of my symptom picture could’ve fitted an endocrinological condition (so ruled out some things). It was similar for other specialities - sometimes, like in rheumatology & later, neurology, things were actually found. It might seem excessive but people are very sick, and this is their life, for the rest of their lives. People deserve to know if some or all of their symptoms, could be caused by something else, and if it’s treatable, to treat it.

Also, I didn’t know this until recently, but doctors should still check for “red flags” which might indicate another illness, during diagnosis. The ME association say this under differential diagnosis: https://meassociation.org.uk/wp-con...early-and-accurate-diagnosis-APRIL-2022-1.pdf

“Indications for carrying out a more detailed assessment and investigation include:

-Atypical symptoms (e.g. joint pain accompanied by swelling)

-Red-flag symptoms or signs (e.g. weight loss, significant lymphadenopathy, fever, focal neurological signs, muscle wasting, generalised pruritis/itching skin, dry eyes and mouth)”

I had my diagnosis confirmed by an ME specialist on the NHS (known to be very sympathetic to ME patients, so not someone who is dismissive) when I became more unwell, a few years back, via phone. But I had 3 or 4 red flag symptoms at the time. But they did not ever see me, examine me, ask about those types of symptoms, rule out other conditions or check if there were other conditions in addition to ME, which I think they should always double check, when someone is severely unwell. They relied on the basic blood tests that GPs do. They didn’t see me in person either. (At the time, I would’ve needed hospital transport to see them, which the department wouldn’t provide!) So it wasn’t a thorough diagnosis, even by the ME association’s standards, & it shouldn’t be happening. But I think it still is happening - this is normal for ME diagnosis.

I don’t think the differential diagnosis that is being done, is good enough. & I hope doctors take more notice of red flag symptoms.

Re your question as to whether it’s a positive diagnosis or not. I think it’s not a positive diagnosis yet, because there’s not a biomarker yet. It is sometimes treated as one (the presence of PEM being unique in ME), but I don’t agree that we can be sure enough of that, or sure enough that we know exactly what PEM is yet, or whether there’s differences between different types of PEM or even possibly fatigue after exertion - not enough to close down all other avenues of investigation. And even if PEM is unique to ME, it doesn’t stop other symptoms being part of another fatiguing condition.

 

Dear @lunarainbows.
I don't think anything I have said is incorrect or inaccurate, although it may not be expressed in such a way to cover the full complexity of the situation. I have tried to point out in several posts that the situation is going to be very complicated.

Nobody doubts that people with mitochondrial disease will get fatigued. They may develop secondary problems once tissue changes are established but by that time one would expect to see signs of that. Moreover, one would expect the primary symptoms to occur during exertion rather than delayed. The whole picture needs to be considered when making a diagnosis.

I would also point out that charitable foundations built up around rare diseases quite often put out material that can be very misleading.

I realise that this is an issue that affects you personally but individual experiences are not a good basis for arguing what causes what. Unfortunately the literature in the public domain these days seems increasingly to be highly unreliable too.

Don't answer if you don't want to but I wondered whether you had a specific mitochondrial diagnosis? If so I will look it up specifically.

 

I agree. They are two different conditions, and most people with ME don’t have it. But, my point is that people with mitochondrial disease can also feel unwell, so it shouldn’t be used as an argument to dismiss mitochondrial research in ME.

As for whether they experience delayed PEM (as a general symptom), I refer you to part of my post above;

“Lets also remember PEM (and finding out if it’s different when it starts immediately / a few hours later, compared to when it starts a few days later) hasn’t even been studied in depth, since it’s only relatively recently that PwME started talking about PEM. People with mitochondrial disease can report crashes, can report feeling very fatigued and tired after activity, and sometimes a slow recovery from that as well.”

So the answer to that is there needs to be more research into different types of exertion or exercise intolerance. Generally everything in papers is written as “exercise intolerance” or “exertion intolerance”. And it’s only relatively recently that PwME themselves started talking in terms of PEM.