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Exercise Testing can rule in/out Mitochondrial Myopathy

Discussion in 'Diagnostic Guidelines and Laboratory Testing' started by BeautifulDay, Nov 8, 2017.

  1. BeautifulDay

    BeautifulDay Senior Member

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    This conversation is likely of interest to many here. I wrote it to @Valentijn because she previously expressed an interest in exercise testing.

    Hi @Valentijn, At one point you mentioned you were interested in what I learned at the Mitochondrial Conference. Dr. Rajeev Bhatia's presentation on "Exercising Testing in Mitochondrial Disorder -- Unmasking the Defect" was very interesting. Specifically, how exercise testing is used as a test to rule in or rule out mitochondrial myopathy and that it was also useful in monitoring therapy (such as Mito Cocktail supplements and medication trials).

    Dr. Rajeev Bhatia's study results reflect exactly what was recently found when our local pulmonologist did the exercise test on our 19 year old daughter. She did the bike test (but it can also be treadmill). They pinched her nose and had her breathe through a tube. They found her peak exercise capacity is reduced (with a maximum oxygen uptake, or VO2, of 61% of the predicted value for a healthy person of her age and size). In addition, there were additional abnormalities that are consistent with mitochondrial disease, including an early-onset anaerobic threshold, a somewhat overly brisk rise in her heart rate, and a borderline-low value of the peak oxygen pulse.

    All of the findings on my daughter matched with Dr. Rajeev's findings on his patients. They are sending my daughter for an echocardiogram to rule out any heart issues that can cause this. Otherwise, these results are just another indication that she has Mitochondrial Disease. We know the echocardiogram will come out fine since she has had these in the past.

    They will now be testing our entire MitoD family with the same exercise test.

    Since some of our symptoms are similar (yours and mine including exercise induced asthma), it's possible that such an exercise test could help determine if your Chronic Fatigue is also caused by Mitochondrial Disease. Not all mutations are known yet, but it looks like this CPET test along with ruling out heart issues is a strong indication of MitoD. Of course, MitoD can also cause heart issues, so having similar results to my daughter plus heart issues, does not necessarily rule out MitoD.

    Over and over again at the conference was the fact that many MitoD patients go from aerobic to anaerobic too quickly. Once in anaerobic, even the best athletes can only keep going for just a few minutes. Therefore, those of us who get winded doing dishes and walking up stairs and have to lay down to catch our breath -- it could be a mitochondrial issue.
     
    Last edited: Nov 8, 2017
  2. ryan31337

    ryan31337 Senior Member

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    Hi @BeautifulDay,

    Thanks for sharing. I've done 3x CPETs and was also keen to learn how they could inform further investigation.

    There is a very good write up found on this blog: https://www.pftforum.com/blog/diagnosing-mitochondrial-myopathies/ - the guy that wrote that runs an exercise physiology clinic and very kindly reviewed my results when I sent them to him.

    In summary the key points to look out for are:
    • reduced maximum VO2
    • elevated Ve/VO2
    • early Anaerobic threshold
    • elevated RER
    • normal maximum heart rate
    • elevated chronotropic index
    • reduced PETCO2
    • normal blood pressure
    All of those can happen due to other cardiovascular diseases too though, so to differentiate you need invasive testing (not routinely done) to also see the following in MM:
    • normal cardiac output
    • reduced arterial-venous O2 content difference
    • elevated blood lactate
    However its still only indicative, not definitive. I have seen POTS literature also show similar reduced VO2max, elevated VE/VO2, hyperkinetic circulation and reduced arteriovenous O2 content difference. The assumption being its due to a local O2 delivery problem rather than poor actual O2 utilisation in the cells as per MitoD. When I had a CPET as part of POTS investigations I fit the bill for MM, but my local physiologist was much quicker to lay the blame on 'just POTS'...

    Its also worth noting that research has shown the MitoD spectrum to be very broad, 1x study showed confirmed MM patients scoring anywhere between 30% and 90ish% (normal) of predicted VO2max, with other markers like elevated blood lactate being marginal or normal for some patients during testing too.
     
    Last edited: Nov 8, 2017
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  3. lnester7

    lnester7 Seven

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    But that happens in Cfs too. So how do you know is Cfs vs a MitoD where the mutation is still unknown?
     
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  4. ryan31337

    ryan31337 Senior Member

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    As far as I know the CPET findings in CFS relate to abnormalities found only on repeat (day 2) testing. The findings in MM and POTS are from single tests.
     
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  5. BeautifulDay

    BeautifulDay Senior Member

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    Thanks @ryan31337

    I'm heading out the door with kids in a few minutes and won't be back until later. However, I've skimmed the links (and the links within the article) and it's all very interesting and I need to go back and do a deeper dive. Thank you for the link.

    Within our family we had the diagnosis of Chronic Fatigue Syndrome with various other symptoms between the family members. My teen daughter and I have POTS. My POTS turned into low pulse pressure as I got older. My heart is too tired in my 40's to tachycardia any more.

    In the last year, it was discovered that those in our family with all these weird symptoms had a mutation that causes Mitochondrial Disease (dominant mutation - takes only one). That's when the Mitochondrial Clinic started studying our family. I believe there are others here with Chronic Fatigue and POTS who also may have Mitochondrial mutations. I don't believe all Chronic Fatigue patients are MitoD, but some of them may be like our family members. There might be a few others who have Secondary Mitochondrial Dysfunction on PR.

    I look forward to fully reading your links and information. Everything in the field is changing very quickly. Muscle biopsy used to be the gold standard. Now it's finding the mutations.
     
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  6. ryan31337

    ryan31337 Senior Member

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    In complete agreement with you @BeautifulDay.

    You were very helpful a little while ago in sharing your family symptoms with me and it spurred me on to seek some advice from a neuromuscular/mito aware clinic. I'm pleased to say I saw a good doc and a muscle biopsy is on the radar if nothing comes of preliminary bloods and nerve conduction studies :)
     
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  7. ryan31337

    ryan31337 Senior Member

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    Do you have any good summary links for finding mutations?
     
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  8. TenuousGrip

    TenuousGrip Senior Member

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    I'll be watching this thread very closely ... particularly since I leave in a very few days for Boston to undergo Invasive Cardiopulmonary Exercise Testing in the clinic of Dr. David Systrom, at Brigham and Women's Hospital.
     
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  9. lnester7

    lnester7 Seven

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    In Cfs, if you do the excercise test ( in not so disabled patients) you will find the low AT also.
    Now you will see reduce capacity from day one to 2.
    Now they say 30% of Cfs patients have POTs so might be for Cfs just the POTs partients qualify.
    My AT was 115BPM very reduce for my age. But again I have POTs and top of cfs.
     
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  10. ryan31337

    ryan31337 Senior Member

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    Lower AT is normal for healthy but inactive people that don't engage in exercise, which also covers most of us.

    The important findings in the 2 day studies was as you say, the unexplained drop in functioning on second test.
     
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  11. ryan31337

    ryan31337 Senior Member

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    Cool. There was another member of phoenix rising that did this. He got a the diagnosis of POTS with pre-load failure, as per Systrom's research.

    Unfortunately I don't think any of their interventions were that helpful in his case, I hope you have better luck.
     
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  12. TenuousGrip

    TenuousGrip Senior Member

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    Yeah. I think you're right.

    But -- like lots of us -- I'm at the point where I want the best/most correct diagnosis possible, even if it doesn't immediately lead to an effective treatment.

    Thanks for the well-wishes.
     
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  13. BeautifulDay

    BeautifulDay Senior Member

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    This is best database I know of for mutations related to Mitochondrial Disease.
    https://mseqdr.org/index.php

    At the Mito Conference the doctors were speaking about how they try to keep adding to the database, but with new research coming out daily, they agreed it's not quite up to date with what it known. In addition, they are always on the lookout for new mutations. That is mutations that are causing similar symptoms maybe next to an already known mutation.
     
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  14. BeautifulDay

    BeautifulDay Senior Member

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    A presenting Mito Doctor at the conference mentioned how the doctors doing the muscle biopsy must follow the instructions exactly. He once had a surgeon who saw that the biopsy was supposed to be immediately frozen but thought he knew better and when the Mito doctors looked at the specimen it was all burned up from the alternate procedure used by the surgeon.

    While we all find doctors who don't listen to us -- nothing like being diagnosed with something without the doctor fully comprehending or listening to our full length of symptoms. It's just as troubling to hear that doctors even run into other doctors who don't listen to them.
     
  15. BeautifulDay

    BeautifulDay Senior Member

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    The study of Primary Mitochondrial Disease and Secondary Mitochondrial Dysfunction is still in it's infancy. There are many people for which doctors today don't yet have the tools or knowledge to diagnose. Take for example mutations being the gold standard for diagnosis today, yet just a few years ago it was muscle biopsy. Yet, the doctors agree, that most of the mutations are still unknown to them and muscle biopsy is still a very useful tool.

    One of the excellent presenters at the conference, Dr. Charles Hoppel who spoke on "What is the State of Functional Mitochondrial Testing" made some fabulous discoveries. He has found that some of the cases where Mitochondrial Disease is believed to exist, yet the muscle biopsy didn't show it was -- was because the researchers were only looking very tight in on the mitochondria. He presented that the researchers also need to look at these biopsies from a step further back.

    He presented slides where patients had Mitochondrial Disease, but the string of connected mitochondria were not where they were supposed be (not next to what they were supposed to be feeding energy to). But instead the line of interconnected mitochondria was over farther. Definitely an issue with Mitochondria, but not something picked up on the typical analysis of muscle biopsy where researchers look tight in on a mitochondria.

    Muscle Biopsy - mitochondria.jpg

    This doctor wants doctors to remember to not only look close in at these biopsies, but look at them from a little farther distance too.

    It would be nice to live in a time when all of these things were already known and they could just check off a list. Instead, we are living in the age of discovery where new items regarding Mitochondrial Disease are being found every day.

    I find it hopeful that all these great researchers are looking for answers for us. But it also means that we need to keep the pressure on our own doctors, ask about the latest techniques, and keep challenging them to keep up with the ever evolving field.

    One field that provides hope for the currently undiagnosed is muscle biopsy with fibroblast and electron microscopy. I do wish it would move along faster, yet, I am very pleased that there are doctors such as Dr. Charles Hoppel who view the field as something still with vasts amounts still to be explored and discovered. His references throughout to Star Wars and Yoda were fabulous.
     
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