Cerebral blood flow remains reduced after tilt testing in myalgic encephalomyelitis/chronic fatigue syndrome patients

[nerd]

Published: 23 September 2021
Authors: C. Linda M.C. van Campen, Peter C. Rowe, Frans C. Visser
doi: 10.1016/j.cnp.2021.09.001

Highlights

• Cerebral blood flow in ME/CFS patients remains abnormal 5 minutes post-tilt test.
• Post cerebral blood flow abnormalities do not depend on hemodynamic results and on end-tidal carbon dioxide pressures during the tilt-test.
• Post cerebral blood flow abnormalities are most severe in more severely diseased ME/CFS patients.

Abstract

Objective
Orthostatic symptoms in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) may be caused by an abnormal reduction in cerebral blood flow. An abnormal cerebral blood flow reduction was shown in previous studies, without information on the recovery pace of cerebral blood flow. This study examined the prevalence and risk factors for delayed recovery of cerebral blood flow in ME/CFS patients.

Methods
60 ME/CFS adults were studied: 30 patients had a normal heart rate and blood pressure response during the tilt test, 4 developed delayed orthostatic hypotension, and 26 developed postural orthostatic tachycardia syndrome (POTS) during the tilt. Cerebral blood flow measurements, using extracranial Doppler, were made in the supine position pre-tilt, at end-tilt, and in the supine position at 5 minutes post-tilt. Also, cardiac index measurements were performed, using suprasternal Doppler imaging, as well as end-tidal PCO2 measurements. The change in cerebral blood flow from supine to end-tilt was expressed as a percent reduction with mean and (SD). Disease severity was scored as mild (approximately 50% reduction in activity), moderate (mostly housebound), or severe (mostly bedbound).

Results
End-tilt cerebral blood flow reduction was -29 (6)%, improving to -16 (7)% at post-tilt. No differences in either end-tilt or post-tilt measurements were found when patients with a normal heart rate and blood pressure were compared to those with POTS, or between patients with normocapnia (end-tidal PCO2 ≥30 mmHg) versus hypocapnia (end-tidal PCO2 <30 mmHg) at end-tilt. A significant difference was found in the degree of abnormal cerebral blood flow reduction in the supine post-test in mild, moderate, and severe ME/CFS: mild: cerebral blood flow: -7 (2)%, moderate: -16 (3)%, and severe :-25 (4)% (p all <0.0001). Cardiac index declined significantly during the tilt test in all 3 severity groups, with no significant differences between the groups. In the supine post-test cardiac index returned to normal in all patients.

Conclusions
During tilt testing , extracranial Doppler measurements show that cerebral blood flow is reduced in ME/CFS patients and recovery to normal supine values is incomplete, despite cardiac index returning to pre-tilt values. The delayed recovery of cerebral blood flow was independent of the hemodynamic findings of the tilt test (normal heart rate and blood pressure response, POTS, or delayed orthostatic hypotension), or the presence/absence of hypocapnia, and was only related to clinical ME/CFS severity grading. We observed a significantly slower recovery in cerebral blood flow in the most severely ill ME/CFS patients.

Significance
The finding that orthostatic stress elicits a post-stress cerebral blood flow reduction and that disease severity greatly influences the cerebral blood flow reduction may have implications on the advice of energy management after a stressor and on the advice of lying down after a stressor in these ME/CFS patients.

 

[Rufous McKinney]

What the heck does this mean?

"reduction may have implications on the advice of energy management after a stressor and on the advice of lying down after a stressor in these ME/CFS patients."

 

[SNT Gatchaman]

What the heck does this mean?

"reduction may have implications on the advice of energy management after a stressor and on the advice of lying down after a stressor in these ME/CFS patients."

I'm interpreting as advice on pacing. I.e. if you would usually rest after an activity as part of your pacing, then resting while lying down may be better than simply resting while sitting.

Alternatively, we may need to become bats.

 

[nerd]

I'm interpreting as advice on pacing. I.e. if you would usually rest after an activity as part of your pacing, then resting while lying down may be better than simply resting while sitting.

No idea what they really mean but my personal experience is that I'm doing better when I shift between the stages slowly, so not directly try to stand up from a lying position or lie down from a standing position, but intermediately sit down for a few minutes.

 

[SNT Gatchaman]

One of my pet theories at the moment is that there's a vicious cycle going on with orthostatic intolerance. Tying in to Younger and vanElzakker's work on neuroinflammation and Blitshteyn's description of a neurological cause of POTS, I'm currently thinking of it as:

There does seem to be evidence for each step that indicates the potential for such reinforcement. Also, OI and CBF alone can self-reinforce, as Blitshteyn describes:

• Impaired cerebral blood flow can result in structural and functional changes in the cortex and brainstem, altering the central autonomic networks and resulting in increased sympathetic outflow

But I think the neuroinflammation component is important, not least to explain the symptom spectrum we experience (brain fog, hypersensitivity etc).

I expect there's more than one such vicious cycle at play in ME/CFS of course, which might explain why it's hard to spontaneously recover.

 

[Rufous McKinney]

I got additionally stuck on the 60 ME people. Thirty have normal HR and BP. But they are none the less experiencing reduced cerebral blood flow, also? Is that correct?

 

[Violeta]

Thank you, @nerd, this is interesting, and explains the way I feel when I get out of bed in the morning.

I would imagine it has something to do with adrenergic receptors. I don't know enough about them, but just looking around a bit, I would think it has to do with alpha 1 adrenergic receptors, and agonists for it would be what would be needed.

Does anyone have a clue what the cause is? Lack of adrenaline?

I edited alpha 2 adrenergic receptors to alpha 1 adrenergic receptors.
Alpha 2 receptor agonists lower blood pressure.
Alpha 1 adrenergic receptor agonists raise blood pressure.
I need to keep reading.

 

[Pyrrhus]

Related discussions:

Reductions in Cerebral Blood Flow Can Be Provoked by Sitting in Severe Myalgic Encephalomyelitis... (Van Campen et al. 2020)
https://forums.phoenixrising.me/thr...ncephalomyelitis-van-campen-et-al-2020.81574/

Cerebral Blood Flow Is Reduced in Severe ME/CFS during a 20 degrees head up tilt test (Van Campen et al 2020)
https://forums.phoenixrising.me/thr...ead-up-tilt-test-van-campen-et-al-2020.80444/

 

[Violeta]

This morning I took Butcher's Broom an hour before getting up and staying up and when I had to get up I didn't feel as bad as usual. I also put on compression socks when I get up, and those help, too.

Butcher's Broom is an alpha-1 adrenergic receptor agonist.

Ruscus aculeatus is an alpha-adrenergic agonist that causes venous constriction by directly activating postjunctional alpha1- and alpha2-receptors, in turn stimulating the release of noradrenaline at the level of the vascular wall. It also possesses venotonic properties: it reduces venous capacity and pooling of blood in the legs and exerts protective effects on capillaries, the vascular endothelium, and smooth muscle. Its flavonoid content strengthens blood vessels, reduces capillary fragility, and helps maintain healthy circulation

https://pubmed.ncbi.nlm.nih.gov/11152059/

 

[Learner1]

My autonomic neurologist prescribed pyridostigmine, neostigmine, and Huperzine A for this problem, as well as a beta blocker.

I'm on Huperzine A now, as pyridostigmine has allergens and can no longer be compounded, while neostigmine had too short a half life.

 

[perrier]

This morning I took Butcher's Broom an hour before getting up and staying up and when I had to get up I didn't feel as bad as usual. I also put on compression socks when I get up, and those help, too.

Butcher's Broom is an alpha-1 adrenergic receptor agonist.

Ruscus aculeatus is an alpha-adrenergic agonist that causes venous constriction by directly activating postjunctional alpha1- and alpha2-receptors, in turn stimulating the release of noradrenaline at the level of the vascular wall. It also possesses venotonic properties: it reduces venous capacity and pooling of blood in the legs and exerts protective effects on capillaries, the vascular endothelium, and smooth muscle. Its flavonoid content strengthens blood vessels, reduces capillary fragility, and helps maintain healthy circulation

https://pubmed.ncbi.nlm.nih.gov/11152059/

what dose did you take? thanks for posting the article.

 

[Violeta]

what dose did you take? thanks for posting the article.

You're welcome!

I take 2 500mg capsules in the morning. I have tried taking one at night, but haven't done that often enough to see if it makes a difference. I did sleep well that night, though.

 

[Violeta]

I'm trying bacopa monnieri and finding it very helpful. I have seen studies that explain why it helps with symptoms, but am still looking to see if it actually gets to the root cause.

"Increases blood flow"

Here's one study that explains how it helps with ammonia issues. Ammonia isn't the only cause of orthostatic hypotension, so it may not be the answer for everyone.

https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC4564645/

 

[Consul]

Related new article from Carmen Scheibenbogen
https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-021-03143-3

 

[GlassCannonLife]

I got additionally stuck on the 60 ME people. Thirty have normal HR and BP. But they are none the less experiencing reduced cerebral blood flow, also? Is that correct?

Yes I believe so. I didn't check if they specify, but I assume those are the mild patients. I didn't have POTS until I became severe but still found lying down would make me feel better much faster than resting sitting up etc

 

[Rufous McKinney]

I didn't have POTS until I became severe but still found lying down would make me feel better much faster than resting sitting up etc

I didn't have noticeable POTS while mild, either....but definitely had alot of that during an episode of extreme worsening....

 

[GlassCannonLife]

Related new article from Carmen Scheibenbogen
https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-021-03143-3

Very interesting, thank you. Shame that they don't provide any theoretical ways to repair endothelial tissues (peptide therapies? ARA-290, GHK-Cu, BPC-157?) or restore a2ar/b2ar functioning (periodic use of agonist/antagonist drugs?).