The two Dutch researchers, C. Linda van Campen and Frans Visser, and Peter Rowe from the U.S., have been on a tear recently. The Van Campen/Visser team (mostly with Peter Rowe) have published 6 ME/CFS studies thus far in 2020, one in 2019 and three in 2018. This is the second of three blogs covering their recent work.
I asked Peter Rowe how a Johns Hopkins researcher came to work so much with the two Dutch researchers. What he said pointed to how valuable in-person conferences can be.
“Frans, Linda, and I met when Sonya Chowdhury and Action for M.E. invited us all to speak on orthostatic intolerance at the UK CFS/ME Research Collaborative 2017 Conference in Bristol, England. Frans and Linda have been collecting data very carefully during tilt testing for several years in their cardiology clinic that specializes in the evaluation and treatment of ME/CFS. Their database is a gold mine of information on changes during tilt, and they are both exceptional physiologists and clinicians.
We thoroughly enjoyed the discussions at the meeting, and wanted to continue working together, so have spent an hour or so on most weekends since 2017 on Skype calls, revising papers and debating how to interpret and present the data. Linda and Frans also traveled to Baltimore for 7-10 days during each of the last two summers, allowing us to work more intensively on research questions and comparing notes on clinical management. On top of all of the scientific productivity, we have a lot of fun working together.
Many ME/CFS clinicians are relatively isolated, especially in the European setting where CBT is still treated as the optimal therapy in some circles, despite the absence of good scientific support for that position. Building this small bridge between practices has been a source of encouragement and insight on both sides of the Atlantic, and we are all pleased that the publications have brought some practical benefits for patients everywhere.”
Van Campen, Rowe and Visser made history when they pretty definitively showed that just about everyone with ME/CFS experiences reduced blood flows to the brain on a tilt table test. If they’re correct, some form of orthostatic intolerance may be as integral to this disease as post-exertional malaise (PEM).
The Brain Fog in Orthostatic Intolerance … err … ME/CFS
Cognitive Function Declines Following Orthostatic Stress in Adults With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Front. Neurocience .2020 Jun 26;14:688. doi: 10.3389/fnins.2020.00688. eCollection 2020.
The group elucidated the universal orthostatic intolerance (OI) theme in another recent study which showed that virtually everyone with ME/CFS gets cognitively challenged when subjected to a tilt test.
This large (n=128) study was composed of people who met the International Consensus definition of ME and the Fukuda criteria. (No healthy controls were included.)
One might have suspected the study was slanted towards people with OI since it was composed of patients suspected of having OI, but besides assessing the usual symptoms associated with OI (dizziness, heart pounding, concentration problems, etc.) the researchers also suspected OI in people experiencing “fatigue, a feeling of weakness, intolerance of low-impact exercise, nausea, abdominal pain, facial pallor, nervousness, and shortness of breath” – which includes just about everyone with ME/CFS.
The participants were given visual N-back tests – which you can do here – just before and within five minutes following the tilt table test.
After being tilted to 70 degrees for a maximum of 30 minutes (for those who could tolerate it that long), the ME/CFS group was separated into categories: those with normal heart rates/blood pressure responses, those with increased heart rates (postural orthostatic tachycardia (POTS) and those with reduced blood pressure (orthostatic hypotension). As in an earlier study the “normal group” was the largest group.
The ME/CFS group made more mistakes on the cognitive tests and took longer to do them after being tilted. (Slowed information processing is a key cognitive finding in ME/CFS.)
The ME/CFS patients with postural orthostatic tachycardia syndrome (POTS) or orthostatic hypotension (OH) didn’t do worse on the cognitive test than the ME/CFS patients without those disorders. Instead – everyone did poorly after being tilted.
The tie that appears to bind the POT and non-POTS patients together is low blood flows to the brain, and very possibly low CO2 levels as well.
Earlier studies may be illuminating what’s happening. They reveal that in the upside down world of ME/CFS/POTS, everything seems to be going in the wrong direction.
Cognitive testing in healthy people results in increased blood flows to their brain but Stewart’s 2012 ME/CFS/POTS tilt table cognitive testing study found that no such increase occurred in ME/CFS patients. Instead, some patients, paradoxically, had reduced blood flows to the brain. Instead of receiving more resources to meet the cognitive challenge, the ME/CFS patient’s brains either got no additional resources or were depleted further.
Plus, the increased vasomotor tone seen in the ME/CFS patients during the tilt table test suggested that the arteries leading to their brain had narrowed reducing blood flows. Here again, the POTS/ME/CFS patients proved to be contrarians: as their arteries constricted during the tilt test, the healthy controls arteries were actually getting larger (vasodilating).
With their brains getting little help – in the form of increased blood flows – and with their blood vessels apparently clamping down as they were tilted thus reducing blood flows – it was no wonder the ME/CFS patients had more trouble doing the the cognitive test following being tilted.
Small Tilts Produce Big Effects in Severe Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
Many people with ME/CFS have problems standing. They may be overt (dizziness, fainting, severe fatigue) or they may be more subtle (increased pain, difficulty thinking and forming words). Standing isn’t the only upright posture that tasks the cardiovascular system, though. As the Bateman Horne Center “hours of upright activity” (HUA) or “feet on the floor” measure indicates, even sitting can cause orthostatic problems.
In the next study “Cerebral Blood Flow Is Reduced in Severe Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients During Mild Orthostatic Stress Testing: An Exploratory Study at 20 Degrees of Head-Up Tilt Testing” Van Campen, Rowe and Visser next showed that a 70 degree tilt table test isn’t needed to provoke plenty of symptoms and a bollixed-up orthostatic response in more severely ill patients. In the these patients simply a 20 degree tilt from a supine position will do just fine.
Being tilted to 20 degrees for 15 minutes resulted in a 27% reduction in cerebral blood flows – a similar percentage to that experienced by more well off ME/CFS patients (26%) during a 30 minute 70 degree tilt table test. A significant reduction in stroke volume index (31%) was again similar to that seen in the healthier ME/CFS group during the longer 30 minute 70 degree test.
Despite the fact that these patients were hardly being tilted up at all, four of the nineteen patients met the definition for POTS. This study makes it clear that even small changes from a supine position can bring on a raft of negative physiological changes in the severely ill.
As they did with the earlier study, the authors suggest that lowered CO2 levels could be narrowing the blood vessels – thus reducing blood flows to the brain. Lowered CO2 levels are associated with hyperventilation or “overbreathing” which refers to a rapid and deep breathing pattern that expels larger than normal amounts of CO2.
A Focus on the Breath?
The author’s one clinical suggestion was that a focus on the depth and speed of the breath could be helpful.
“When hypocapnia is observed, a focus on respiration depth and speed has the potential to be one of the therapeutic guidance options for these patients to lessen orthostatic intolerance complaints.”
- Peter Rowe met Linda Van Campen and Frans Visser at the UK Conference. Since then they’ve worked together on many studies, including six this past year.
- The entire ME/CFS group – whether they had a diagnosis of orthostatic intolerance or not – had reduced blood flows to the brain and reduced CO2 levels upon being tilted to 70 degrees for 30 minutes.
- The entire ME/CFS group – whether they had been diagnosed with postural orthostatic tachycardia syndrome (POTS) or not – displayed markedly reduced cognitive abilities after being tilted. They got more answers wrong and took longer to complete the questions.
- The Visser group’s findings suggest that orthostatic intolerance in the form of reduced blood flows to the brain and reduced CO2 levels may be as prevalent in ME/CFS as is post-exertional malaise.
- Severely ill people with ME/CFS only needed to be tilted to 20 degrees for 15 minutes to display the same degree of reduced blood flows and drops in CO2 levels as less ill people with ME/CFS.
- An earlier cognitive study in POTS found that in contrast to the healthy controls, blood flows to the brain did not increase in the POTS patients during the cognitive stressor. Plus, the arteries of POTS patients constricted rather than dilated, as occurred with the healthy controls.
The authors suggested that a focus on breathing depth and speed could be helpful in ME/CFS. That and hyperventilation will be the focus of future blogs.The authors found evidence of hypocapnia, it should be noted, in the broad ME/CFS group (and it was worse in POTS). Hypocapnia is associated with hyperventilation – which has a rather long and somewhat tortured history in ME/CFS dating back to the 1990’s.
Hyperventilation has been found more recently several times in ME/CFS but usually in just a subset of patients. Systrom, for instance, found it in a set of patients during an invasive exercise test. Medow prevented hyperventilation and, in fact, orthostatic intolerance during a tilt table test using phenylephrine.
It’s interesting that hyperventilation is not generally associated with fatigue.
- Check out a home test for hyperventilation here
Hyperpnea, which refers to deeper breathing than normal (without the increased rate of breathing found in hyperventilation), has been found in POTS.
Normal breathing, on the other hand, is often light and relaxed and comes from the diaphragm. If you’ve ever done meditation it’s astonishing how little breath the body needs – sometimes- just wisps of air effortlessly moving in and out of the nose is enough. That type of breathing is inaudible – no wheezing, panting, sighs, deep inhalations or exhalations occur.
Could changing our breathing patterns help?
- Coming Up – a Focus on the Breath
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