Exciting times ahead for our conference in September!
“Pathophysiology and treatment of exertional intolerance in ME/CFS: insights from cardiopulmonary exercise testing”
I think of David Systrom as a hopeful harbinger of the future – not just because of his exciting results – but because of how he came to this field. Systrom was not enticed into it. Instead, he came to it through his study of exercise intolerant individuals – many of whom, he later found out, had ME/CFS.
A pulmonologist working out of Harvard University’s main hospital, he brings two things we vitally need: credibility and contacts. He’s working, for instance, with Anne Oaklander – another Harvard researcher – who uncovered the small fiber neuropathy present in fibromyalgia.
Systrom’s invasive cardiopulmonary exercise test (iCEPT) is like the CPET tests we know, love and occasionally hate – on steroids. Using a catheter, these fantastically expensive tests provide much more information.
Systrom is finding relatively normal VO2 max in ME/CFS – not a surprise for a first day exercise test – but his invasive tests are revealing problems during that first exercise test that ordinary CPET tests cannot. Two major abnormalities are showing up: both the filling pressure of the heart and the systemic oxygen uptake are uniformly low during upright exercise in ME/CFS.
TRAIL Systrome
Systrom propose that the TRAIL pathway provoked by pathogens could be present in ME/CFS.
They suggest the heart is not getting the blood it needs, and the mitochondria are not getting the oxygen they need to produce the energy we need during exercise.
Systrom cited the story of a former competitive cyclist who had undergone a $1,000,000 workup – not that difficult a thing to do, he said, in the hospital he works in – to no avail. His testing revealed the problem – his heart wasn’t pumping the blood it needed to his muscles and even when the blood got there, the oxygen in it wasn’t being transformed into energy.
Systrom also brings the gift of a big data set – something this field has missed for years. Of the 200-plus patients he worked up in one data set, 72% met the criteria for ME/CFS. The man has basically been studying ME/CFS for years. POTS was next on the list (27%), followed by fibromyalgia and mast cell activation syndrome (MCAS) (20%).
This breakdown seems to fits perfectly with the degree of exercise intolerance found in these diseases – present in POTS and FM – but not nearly to the degree found in ME/CFS.
Systrom has identified five different subsets which appear to differ depending on their issues with oxygen extraction and blood vessel problems. The high blood flow group, for instance, has pretty good blood flows but is not using up their oxygen.
Etanercept chronic fatigue syndrome
Dr. Klimas’s drug of choice – Etanercept – knocks down the same immune pathway Systrom’s preliminary results suggest exercise is upregulating in ME/CFS.
Most of this group had ME/CFS and forty percent of them also have small fiber neuropathy (SFN) – a remarkably similar percentage to the amount of SFN found in both POTS and fibromyalgia.
Unfortunately, the amount of small fiber neuropathy present did not correlate with the exercise findings. Systrom, however, believes that small nerve fiber functioning rather than nerve fiber density may be a better measure.
Systrom next surely opened some eyes when he proposed – citing a conversation with another researcher – a new potential immune pathway for ME/CFS called TRAIL. TRAIL involves an uber pro-inflammatory cytokine, TNF-a, that’s often provoked in response to a viral infection. Systrom’s early testing suggests that exercise may be temporarily upregulating that pathway in ME/CFS patients.
A temporary upregulation fits with Nancy Klimas’s model of a massive upregulation of inflammation occurring early in exercise in ME/CFS, which then dysregulates other systems. In fact, Etanercept, the drug Klimas has chosen to tamp down the inflammation in GWI and ME/CFS, is a TNF-a inhibitor (:))
Systrom ended a fascinating presentation with the news that we can expect a treatment study out – something rare in ME/CFS – which shows that pyridostigmine bromide (Mestinon) – at rather increased doses, as I remember, was effective in increasing both VO2 max and, most interestingly, oxygen extraction in the muscles (!).
Mestinon, an old drug, increases the availability of the parasympathetic nervous system neurotransmitter, acteylcholine. Dr. Jay Goldstein recommended it in ME/CFS decades ago but it’s hardly been used in ME/CFS until Systrom came upon the scene.
Check out the story, though, of a person with a longtime case of ME/CFS who is now able to exercise after getting Mestinon (from Systrom).
Systrom is also starting to do muscle biopsies and is incorporating the Seahorse and mitochondrial studies into his work. He has found positive acetylcholine autoantibody results (using the Mayo tests – he has not used the new German tests yet). Also, it’s important to note that all Systrom’s results disappear when the patient is tested while supine. He also noted that the results he’s finding in ME/CFS are not found in deconditioning.
Systrom’s first presentation at an ME/CFS conference was for me the highlight of the conference – not only because he brings such exciting results but because he’s clearly now immersed in this field. His first pure ME/CFS project is being funded through a grant from the Solve ME/CFS Intiative (SMCI).
Systrom has taken exercise testing to a new and exciting level in ME/CFS, but as Dr. Keller, the next presenter, will show, the non-invasive CPET studies are still providing plenty of juice.
Seeking Solutions for ME and Fibromyalgia 
