Interview with Dr. David Systrom (May 5, 2020) on exercise intolerance

[Diwi9]

Video interview with Dr. Systrom entitled: "Pathophysiology of Exercise Intolerance in Chronic Fatigue Syndrome"

 

[pattismith]

This Doc has the best understanding of ME/CFS in my opinion

 

[pattismith]

33mn39 it shows in a cohort ME/CFS of 160 patients

-44% had associated SFN (small fiber neuropathy)
-33% had POTS
-22% had associated Fibro
-22% had associated MCAS
-24% had prior infection

it's clear to me that ME/CFS is a cardiovascular autonomic small fiber neuropathy

 

[Rebeccare]

Thank you for posting this @Diwi9! I'm a patient of Dr. Systrom, and I'll be sure to watch!

What's interesting to me (having not watched even a moment of the video yet), is that is was made by the Osher Center for Integrative Medicine, which is associated Brigham & Women's Hospital (where Dr. Systrom works). The Osher Center is unique because it's associated with a hospital, but it offers acupuncture, cranialsacral therapy, tai chi, and other 'alternative' treatments. Some people might be interested to see the other videos in their 'Grand Rounds' series on their YouTube channel. I'm interested to see what the connection is between their work and what Dr. Systrom is doing.

 

[pattismith]

The video talks about pyridostigmine (42mn04) that may be helpful by modulation of neurovascular function.

@necessary8
we were already discussing about link between SFN and ME/CFS, you may be interested by the video...

 

[Gemini]

Video interview with Dr. Systrom entitled: "Pathophysiology of Exercise Intolerance in Chronic Fatigue Syndrome"

Excellent video. Thanks for posting it @Diwi9!

Like his patient, I've a three decades long ME/CFS history and can relate to her journey.

Glad to hear Dr. Systrom is pursuing a less invasive diagnostic test(s) and would like to see future multi-discipline ME/CFS clinical centers. Agree @pattismith regards his understanding of these aspects of ME/CFS.

He mentions giving a saline infusion, wonder if he's familiar with Drs. Bell/Streeten's low blood volume findings and whether he tests patients for it before the invasive CPET and after Mestinon treatment?

Like the way he characterizes the "functional" problem.

 

[perrier]

33mn39 it shows in a cohort ME/CFS of 160 patients

-44% had associated SFN (small fiber neuropathy)
-33% had POTS
-22% had associated Fibro
-22% had associated MCAS
-24% had prior infection

it's clear to me that ME/CFS is a cardiovascular autonomic small fiber neuropathy

I was not able to determine how severe or mild their ME was. This is very important. Mona, in the interview, was able to walk 3 miles, even before taking mestinon. Also, I note that Dr Systrom feels the side effects are not that severe. Yet, many patients have been unable to use the drug due to the severe side effects. Also, on his treatment slide, I note the use of anti depressants and Ritalin. Dr. Teitelbaum used these decades ago, and saline has been used decades ago. Ritilin just stimulates the system, and a horrific crash can and likely will ensue--for the core problem has not been addressed. Dr Systom's work looks very thorough, and impressive, and what he says was stated by CFS doctors decades ago (perhaps not proved in a lab). I am very worried that the treatment may not really work for many severe patients. I would dearly like to know how sick these patients were before taking mestinon, were they bedridden, or what. What would he propose for the bedridden, I wonder.

 

[Learner1]

Thanks for posting @Diwi9 !

This Doc has the best understanding of ME/CFS in my opinion

I think he understands some great aspects, but is missing a lot. I agree with @perrier and was horrified by his list of "treatments," for example.

it's clear to me that ME/CFS is a cardiovascular autonomic small fiber neuropathy

Er, only 44% had SFN. I've been tested and I don't...


A few thoughts:

Not everyone will be able to take pyridostigmine, due to allergens or side effects. I got it compounded and it did help me stand without being dizzy and exercise. As I raised the dose, the intestinal side effects were miserable.

Due to pharma game playing, the raw ingredient is no longer available for compounding in the US. I tried the sister drug, neostigmine, also compounded, which was effective without the side effects, but the half life was about 4 hours vs 12.

By then, I learned about a supplement, Huperzine A, and consulted with my neurologist on dosing, and tried a 200mg dose. No side effects, and I can stand and exercise.

I also have been taking phosphatidyl choline to repair damaged cell and mito membranes, and I believe it has a synergistic effect, making acetylcholine more available.

I highly recommend autonomic testing, which I was able to do with a dysautonomia specialist, a neurologist. The 4 tests are explained here - he concluded I had hypoperfusion in my brain, which the acetylcholine drugs have helped:

https://www.neuroassociates.us/autonomic-test-preparations.html

What I didn't see in Systrom's testing was metabolic testing that could be easily added to his testing protocol. I recently did it after Dr Kaufman suggested I listen to Peter Attia's interview with Inigo San Millan, a Colorado exercise physiology researcher, who discussed how shifting between carb and fat burning at different points, enables increasing exercise.

https://peterattiamd.com/inigosanmillan/

Looking around the medical community, there was nowhere to get the testing done, but buying a new pair of sports shoes at s local running store, they were able to refer me to a Seattle physical therapist who could do the same testing.

After talking her into letting me do the test, as she was scared I'd collapse, and my neurologist vouching for me that it wouldn't harm me, I did the test first thing in the morning, fasting.

First I put on a heart rate monitor around my chest and was fitted for a mask, similar to the one in the video. It was uncomfortable and squashed my face. It had a big vacuum cleaner type hose to collect all of the metabolites I made as I exhaled. I had to lay on a table for the first 20 minutes to get used to the mask and collect baseline data

Then, the hard part. On a treadmill, I had to pick a speed I could maintain (slower than she thought I should, but one that turned out to be a wise choice) and walk 4 minutes each at grades of 1, 2, 4, 6, 8, 10, and 12%. I stayed at the same speed, but it got increasingly difficult and I was stumbling by the end. The total test was 55 minutes and hard, something I wouldn't have been able to do a year ago, but I've been able to slowly walk 5 miles recently.

My results were abnormal, especially when compared to the athletes they normally see.

• My VO2max was 78% of normal, unlike Mona's
• My top pulse was 105, gated by the beta blocker I take for POTS, even though I was at max exertion
• I was burning carbohydrates at rest, when normal people burn fat
• Though I did burn fat at the easiest intensity, I quickly switched to burning carbs with slight effort. I should have been burning fat a lot longer, and did no have the typical crossover point they see in everyone else

The dietician I followed up with suggested upping my carbohydrates from 30% of calories to 50%. I typically eat 45-50% fat and 20-25% protein, which I've found after much experimentation feels vest for me - if I up carbs, I feel jittery and miserable.

However, he was puzzled by my abnormal burning if carbs instead of fat at rest, and said that the pattern of my results looked more like someone who had blood sugar problems, which I do not (fasting glucose is 80-95 and HbA1C has been 4.2-4.6).

The other explanation for all of this is that I have a fatty acid oxidation problem in my mitochondria, which my recent OAT and NutrEval tests suggest - all my glutaric metabolites were quite high, as they've been in previous tests. The interpretation has suggested low B2 or carnitine, but my carnitine metabolite levels are fine and I'm taking 290mg B2 a day, and there's no way I can be short. Therefore, the remaining explanation is a fatty acid oxidation problem in mitochondria which I'm trying to find someone to help with. I also have below range pyruvate.

I sure wish Systrom would collect other people's metabolites and see if they have similar issues.

Neil McGregor had suggested I had a glycolysis problem (which might lead to the low pyruvate) and less than optimal storage of glycogen in muscles. But, I haven't seen any explanation for why be a body that's given plenty of fat, and should be burning fat, chooses to burn glucose from glycogen when it doesn't have enough. Sure explains my perception of being drained in my arms and legs and my brain giving up when I increase intensity even for as short as 90 seconds.

It seems that they're handling this as a plumbing problem when, for at least some of us, it's a biochemistry and energy production problem.

But it's a good start...

 

[Rebeccare]

This was a good video, and actually helped me understand my own test results much better!

What would he propose for the bedridden, I wonder.

Not everyone will be able to take pyridostigmine, due to allergens or side effects.

I did not do well on mestinon, so he prescribed midodrine instead. Another medication that he considered for me is florinef. I don't know.

However, I don't know if he would propose these medications for people if they are unable to take an exercise test that shows that their exercise intolerance is caused by preload failure as opposed to another issue such as heart failure.

What I didn't see in Systrom's testing was metabolic testing that could be easily added to his testing protocol.

He doesn't do that for everyone, but he noted that my iCPET results indicated metabolic issues. At our next appointment (if and when that ever happens), we were going to discuss some kind of metabolic testing.

The important thing to remember about Dr. Systrom is that he's a pulmonologist. Issues such as inflammation or metabolism are outside of his area of expertise, which is why it's good that ME/CFS research is helping to bring doctors of different specialties together.

 

[Learner1]

don't know if he would propose these medications for people if they are unable to take an exercise test that shows that their exercise intolerance is caused by preload failure as opposed to another issue such as heart failure.

One doesn't need preload failure to have Mestinon, neostigmine or Huperzine A work. Most of us aren't going to have an invasive CPET to find out.

He doesn't do that for everyone, but he noted that my iCPET results indicated metabolic issues. At our next appointment (if and when that ever happens), we were going to discuss some kind of metabolic testing.

The important thing to remember about Dr. Systrom is that he's a pulmonologist. Issues such as inflammation or metabolism are outside of his area of expertise, which is why it's good that ME/CFS research is helping to bring doctors of different specialties together.

Agreed. The problem here is looking at what's happening without getting to the root cause. It seems again like Systrom is looking at it as a plumbing problem, because he's a pulmonologist, a very smart one at that, with lots of resources.

This is definitely a step forward, because we know more than we did before, but if there is a metabolic issue that is causing this to happen, figuring that out would be the key, and then figuring out how to reduce the effect or optimize function. The heart's going to behave in a particular way based on the signals it's getting, which can be biochemical, if mechanical damage is not at the root of it.

Having an interdisciplinary team would be a major step forward. If you can't do it in Boston, it's pretty darn difficult to do anywhere else. Maybe at Stanford. But for the rest of us who live thousands of miles away, we need testing that can get us to answers, so that we can get solutions applied, and even Systrom admits that the invasive CPET test is a business he wants to get out of, because it is so difficult to do, and the effect on patients.

I feel fortunate to have tracked down the metabolic testing that gave me some interesting information That seems to be driving my physical symptoms, but it's really frustrating to have no MD be doing this in my area, no MD interested in analyzing the results, and figuring out what to do about it, and being left on my own to come up with a strategy. And I have a neurologist, I have an ME/CFS specialist, and I actually have a pulmonologist who at the moment is too busy dealing with COVID to think about anything else.

My neurologist is concerned enough about the results that he saw that he is once again going to try to refer me to our local top research universities genetic medicine department who are the only people in town who deal with mitochondrial disorders, but of course they're looking at it as a genetic problem and deal primarily with little children with genetic mitochondrial diseases, and are none too interested in adults with acquired mitochondrial disorders. so the know I got 4 years ago will probably once again be a no and I'll be no farther along.

It sure would be nice if they got something more interdisciplinary started in Boston, and I hope that system could further expand his excellent network of colleagues to address this. Because it's more than just a plumbing problem.

 

[wigglethemouse]

Dr Systrom will be doing Proteomic and Metabolomic plasma iCPET studies per OMF
https://www.omf.ngo/2019/12/02/tripletuesdayomf-spotlight-icpet-study/
and
https://www.omf.ngo/2019/10/23/multi-omics-of-icpet-plasma-samples-study/

 

[Sushi]

This is very important. Mona, in the interview, was able to walk 3 miles, even before taking mestinon.

I believe that she said 1 block before treatment.

Also, on his treatment slide, I note the use of anti depressants and Ritalin.

Those were just on the list that Mona had been prescribed from other doctors--they were not Dr. Systrom's recommendations.

What I didn't see in Systrom's testing was metabolic testing that could be easily added to his testing protocol.

As @wigglethemouse mentioned above, that will come in the next phase.

Having an interdisciplinary team would be a major step forward.

He envisions this--particularly with the collaboration of Dr. Ron Thompson's group at Harvard.

 

[pattismith]

Thanks for posting @Diwi9 !
I think he understands some great aspects, but is missing a lot. I agree with @perrier and was horrified by his list of "treatments," for example.

Er, only 44% had SFN. I've been tested and I don't...

It's bigger than I expected. The great thing with Dr Systrom is that he trusts Dr Oaklander (neurologist that he credited at the end of the video and who made the link between Fibro/ME/CFS and SFN with some others).
It may be that not all the ME/CFS patients have SFN but it may also be (I am not the only one that think that way) that a lot of autonomic SFN patients are not correctly diagnosed with a skin biopsy...

 

[perrier]

I believe that she said 1 block before treatment.
Those were just on the list that Mona had been prescribed from other doctors--they were not Dr. Systrom's recommendations.
As @wigglethemouse mentioned above, that will come in the next phase.
He envisions this--particularly with the collaboration of Dr. Ron Thompson's group at Harvard.

Actually,I just reviewed the video: Dr Systrom showed a black panel with what were called alternative therapies, which he called complimentary therapies. He went over them point by point. He said these were found in the CFS literature and used. He did not disagree with any of the therapies.

my comment: these therapies are decades old, and many CFS doctors have used these, along with saline. Stimulating the system leads of horrific crashes, as many patients can attest. Many patients have tried these alternative therapies to no avail. These alternative therapies can be found in Dr Teitelbaum's old book: From Fatigued to Fantastic.

Mestinon has resulted in many severe side effects.

I am grateful to Learner for pointing out the perhaps there are other alternatives to Mestinon.

Sadly, there are many pieces of the puzzle on the table; and these pieces have not been assembled. The research is at the moment Fragmented. And if it continues this way, then patients will continue to suffer for more decades. Yes, a whole diagnostic unit is required to help these patients. How many years before that gets off the ground?

I recognise that my position is not a popular one. But there are some young people who are suffering horrifically, and who are barely holding on.

Dr Systrom looks very bright, and very thorough, but he needs a larger team around him.

 

[Learner1]

Dr Systrom showed a black panel with what were called alternative therapies, which he called complimentary therapies. He went over them point by point. He said these were found in the CFS literature and used. He did not disagree with any of the therapies.

my comment: these therapies are decades old, and many CFS doctors have used these, along with saline. Stimulating the system leads of horrific crashes, as many patients can attest. Many patients have tried these alternative therapies to no avail. These alternative therapies can be found in Dr Teitelbaum's old book: From Fatigued to Fantastic.

You're right. That list was extremely disappointing. There are many other more useful therapies that aren't on that ioutdated list.

I am grateful to Learner for pointing out the perhaps there are other alternatives to Mestinon.

You're welcome! I'm actually thrilled that I had to go off it, as the side effects were unpleasant. Happy to find Huperzine A.

Yes, a whole diagnostic unit is required to help these patients. How many years before that gets off the ground?

I recognise that my position is not a popular one. But there are some young people who are suffering horrifically, and who are barely holding on.

Dr Systrom looks very bright, and very thorough, but he needs a larger team around him.

It's like the 3 proverbial blind men looking at an elephant. We need about 25 of them working together to get comprehensive testing, analysis and treatment. Now, not in 10 years... There are a lot of valid tests and tools today. It would be nice if doctors used them and coordinated.

 

[ShepherdK]

You're welcome! I'm actually thrilled that I had to go off it, as the side effects were unpleasant. Happy to find Huperzine A.

+1 for Huperzine A.

I cycle this one (3-4 days on, 1-2 days off @ 200mcg) - taking too much tends to negatively impact my sleep. It works by inhibiting acetylcholinesterase - which leads to an eventual buildup of acetylcholine. ME/CFS patients have increased autoantibodies to acetylcholine, which leads to the depletion of this pretty essential neurotransmitter.

As for the video - I agree with Learner1 here - they are dancing around the core problem, which means the therapies will be very hit-or-miss. I actually think we are getting very close to a definitive cause for a major subset of ME/CFS based on the PDP1/SOD2 findings in the Prusty/Naviaux research.

 

[Sushi]

Actually,I just reviewed the video: Dr Systrom showed a black panel with what were called alternative therapies, which he called complimentary therapies. He went over them point by point. He said these were found in the CFS literature and used. He did not disagree with any of the therapies.

I believe he was listing these common therapies (which most of us have tried) just as background. He is not (and doesn't claim to be) an ME/CFS specialist--he came to the connection with ME/CFS fairly recently and almost by accident when he discovered in his research that he was getting a lot of patients who met the criteria for an ME/CFS diagnosis--he wasn't seeking such patients.

I believe he is trying to develop a team approach to contribute to the aspect of the research that his background as a pulmonologist and critical care physician most qualify him for. He keeps reminding us of this background and that he can only contribute in certain areas. I think he has discovered one part of a very complex puzzle--and yes, it may be downstream, but his research was not originally focused on our patient community.

 

[Diwi9]

@ShepherdK - I recently tapered off of most of my prescriptions, trying to identify the source of certain side effects. I'm falling asleep much easier since stopping Mestinon...and deleted some other negative side effects too. I going to pull out my Huperzine A and see if I can cycle and see how it goes.

 

[Sushi]

I've been cycling Mestinon for a few months and get unexpected effects. Once I got past the gastric side-effects I noticed that my sinuses cleared up amazingly--but it didn't last more than a few weeks and then the infections came back. So I've been cycling on and off it trying to either find a sweet spot or an effective cycle pattern. It raises the question for me as to how acetylcholine might affect sinuses (which are a major symptom for many of us)? I see that at least one other person is experimenting with cycling. I am wondering if there is an optimal daily dose or whether cycling itself has a therapeutic effect?

I cycle this one (3-4 days on, 1-2 days off @ 200mcg)

 

[Gemini]

It sure would be nice if they got something more interdisciplinary started in Boston, and I hope that system could further expand his excellent network of colleagues to address this. Because it's more than just a plumbing problem.

Agree @Learner1.

Interestingly Dr. Systrom was interviewed two years ago by Llewellyn King and mentioned the possible method of action of Mestinon in ME/CFS and an interdisciplinary research team in Boston [23:12 on video] :