ME/CFS Patients with Joint Hypermobility Show Larger Cerebral Blood Flow Reductions during Orthostatic Stress Testing... (van Campen et al., 2021)

[Pyrrhus]

The Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients with Joint Hypermobility Show Larger Cerebral Blood Flow Reductions during Orthostatic Stress Testing Than Patients without Hypermobility: A Case Control Study
Hypermobility in ME/CFS: effect on cerebral blood flow (van Campen, Rowe, and Visser, 2021)
https://esmed.org/MRA/mra/article/view/2494


Main points:

• People who have joint hypermobility may have problems with collagen, the substance that provides strength and elasticity to joints in the body.
• Since collagen is also used by the body to provide strength and elasticity to blood vessels, any dysautonomic condition of blood vessels might be exacerbated by an insufficiently strong collagen layer surrounding the blood vessels.
• Therefore, the presence of joint hypermobility might suggest a worse dysautonomic condition of blood vessels than that found in people without joint hypermobility.
• Since a dysautonomic condition of blood vessels leads to a reduction in blood flow to the brain while standing, people with joint hypermobility might have an even greater reduction in blood flow to the brain while standing.
• The authors tested this possibility and concluded that ME/CFS patients with joint hypermobility have larger reductions in blood flow to the brain during orthostatic stress testing than patients without hypermobility.

Related discussions:

• Endothelial Dysfunction in ME
• Insights from Invasive Cardiopulmonary Exercise Testing of Patients with ME/CFS (Joseph et al., 2021)

Excerpt:

Aims:
An abnormal reduction in cerebral blood flow (CBF) during orthostatic stress is common in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a condition with more prevalent joint hypermobility than in the healthy population. As one of proposed underlying mechanisms of orthostatic intolerance in hypermobile patients is vessel laxity, reducing the normal return of blood to the heart during orthostatic stress, we hypothesized that the CBF reduction during tilt-testing would be larger in ME/CFS patients with joint hypermobility than in patients without hypermobility.

Methods:
In this case-control study, 100 female ME/CFS cases with joint hypermobility, who had undergone tilt-testing with CBF measurements, were compared to 100 female ME/CFS patients without joint hypermobility, matched by age and disease duration.

Results:
No differences in baseline characteristics were found between groups. The hypermobile patients had significantly more postural orthostatic tachycardia syndrome (POTS) during tilt testing than the non-hypermobile ones. Compared to supine CBF, the degree of CBF reduction during the tilt was significantly larger in hypermobile cases than in the non-hypermobile controls: -32 (6)% vs -23 (7)% (p<0.0001) The larger CBF reduction in hypermobile patients was not only present in POTS patients: -33 (6)% vs -24 (4)%, but also in patients with a normal heart rate and blood pressure response to tilt testing: -31 (6)% vs -22 (9)%: (both p<0.0001).

Conclusions:
ME/CFS patients with joint hypermobility syndromes have larger CBF reductions during orthostatic stress testing than patients without hypermobility. This larger CBF reduction is independent of the heart rate and blood pressure results of the orthostatic stress test.

 

[kangaSue]

A simple way to improve the blood flow could be to just do acute beetroot juice supplementation. Not just for cerebral blood flow though, this can help on a more systemic basis as well so can aid with both improved oxygenation of muscles, and autonomic dysfunction that is rife in these conditions too.
https://www.sciencedirect.com/science/article/abs/pii/S0195666312003248
https://pubmed.ncbi.nlm.nih.gov/28476923/
https://franklincardiovascular.com/nitric-oxide-in-promoting-healthy-autonomic-function/

 

[Pyrrhus]

A simple way to improve the blood flow could be to just do acute beetroot juice supplementation.

I'm not sure what that is supposed to accomplish, but if it acts as a vasodilator, that could worsen the blood flow to the brain.

Remember that the problem is due to veins in the legs that fail to constrict upon standing. A vasodilator might worsen the blood pooling in the legs, further reducing the blood flow to the brain. This is why people often use compression stockings on their legs to improve blood flow to the brain.

 

[kangaSue]

Remember that the problem is due to veins in the legs that fail to constrict upon standing.

From what I read into it, that's something of a misconception though as you can't just have a state of impaired vasoconstriction. The larger issue is one of autonomic dysfunction with the small vascular resistance vessels (arterioles) being unable to properly regulate between the vasodilation and vasoconstriction responses at the appropriate time, something which involves vagal nerve function, and nitric oxide increases the vagal tone in the body.

The different vascular beds can regulate themselves independently of each other, but brain hypoperfusion can be because of a reduced blood volume being circulated from the lower extremities due to splanchnic pooling because of impaired mesenteric resistance vessel function, and vagus nerve dysfunction can have a hand in this - low grade coeliac plexus inflammation can be one thing involved, hands up all those who have gut issues? Adding exercise into this mix is another factor that can further exacerbate this situation.

Not quite sure of all the mechanisms involved in it but as I understand it, the paradox is that a nitric oxide vasodilator can help to better balance out the issue of small vessel dysregulation, but that may only be in cases that don't have an involvement of multiple vascular beds narrowing, such as can apply to those with connective tissue disorders and joint hypermobility.

 

[Pyrrhus]

The larger issue is one of autonomic dysfunction with the small vascular resistance vessels (arterioles) being unable to properly regulate between the vasodilation and vasoconstriction responses at the appropriate time, something which involves vagal nerve function, and nitric oxide increases the vagal tone in the body.

I think you might be confusing two very different types of endothelial dysfunction here:

1. First, you can have a dysfunction of the autonomic nerves that control dilation and constriction of the blood vessels. This type of dysautonomia results in orthostatic intolerance and exercise intolerance. (but not necessarily PEM)
2. Second, you can have a dysfunction of the ability of the endothelial cells to release nitric oxide when necessary to stimulate vasodilation, which is a purely localized response.

For more information, see these discussions:

• Endothelial Dysfunction in ME
• Insights from Invasive Cardiopulmonary Exercise Testing of Patients with ME/CFS (Joseph et al., 2021)

 

[Oliver3]

I think you might be confusing two very different types of endothelial dysfunction here:

1. First, you can have a dysfunction of the autonomic nerves that control dilation and constriction of the blood vessels. This type of dysautonomia results in orthostatic intolerance and exercise intolerance. (but not necessarily PEM)
2. Second, you can have a dysfunction of the ability of the endothelial cells to release nitric oxide when necessary to stimulate vasodilation, which is a purely localized response.

More information:

• Endothelial Dysfunction in ME
• Insights from Invasive Cardiopulmonary Exercise Testing of Patients with ME/CFS (Joseph et al., 2021)

This is extremely disheartening. How do you change a genetic flaw like that except through some distant CRISPR dream

 

[kangaSue]

First, you can have a dysfunction of the autonomic nerves that control dilation and constriction of the blood vessels. This type of dysautonomia results in orthostatic intolerance and exercise intolerance. (but not necessarily PEM)

Yeah, I get what you're saying and I was thinking more of POTS than PEM when I made my comment. Which ever way we care to spin it though, it's an impaired vasodilation vasoconstriction response affecting skeletal muscles that causes PEM is it not? Even if it happens to be driven by something like autoantibodies against ß2-adrenergic receptor;
https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-021-02833-2
[ Our hypothesis considers ME/CFS as a disease of a dysfunctional autonomic nervous system (ANS) resulting from sympathetic overactivity in the presence of dysfunctional ß2AdR and endothelial dysfunction. The combined disturbance leads to a disruption of the physiological interaction between skeletal muscles and the cardiovascular system. High sympathetic tone in the presence of vascular dysfunction may lead to an excessive vasoconstrictor stimulus in the brain and skeletal muscles, which in the latter is counter-regulated by the metabolically stimulated generation of endogenous vasodilators in the physiological process of functional sympatholysis. ]

Second, you can have a dysfunction of the ability of the endothelial cells to release nitric oxide when necessary to stimulate vasodilation, which is a purely localized response.

Something I have noticed in many chronic conditions is that the pathology invariably also involves some degreee of nitric oxide synthase deficiency.

 

[Pyrrhus]

Which ever way we care to spin it though, it's an impaired vasodilation vasoconstriction response affecting skeletal muscles that causes PEM is it not?

It certainly seems likely that this impairment in vasoconstriction/vasodilation (endothelial dysfunction) and the resultant cardiovascular exercise intolerance might lead to microstructural damage or disturbed cellular metabolism in muscle cells that would contribute to PEM.

But the symptoms of PEM, especially the neurological ones, make me think that there is much more to the phenomenon of PEM than simply the downstream effects of cardiovascular exercise intolerance...

Something I have noticed in many chronic conditions is that the pathology invariably also involves some degreee of nitric oxide synthase deficiency.

Yes quite possibly- you may be interested in this post:
https://forums.phoenixrising.me/threads/endothelial-dysfunction-in-me.83521/#post-2332501

 

[Pyrrhus]

Related discussions:

Signs of Intracranial Hypertension, Hypermobility, and Craniocervical Obstructions in Patients With ME/CFS (Bragee et al., 2020)
https://forums.phoenixrising.me/thr...l-obstructions-in-patients-with-me-cfs.81446/

Neurological and spinal manifestations of the Ehlers–Danlos syndromes (Henderson et al., 2017)
https://forums.phoenixrising.me/thr...m-surrounding-peripheral-nerves-in-eds.77638/

 

[Hufsamor]

Theres nothing to do with this, is it?

( I’ve got hyper mobility and I’ve measured a very bad back flow of blood from my ankles…those papers explained a lot. I didn’t get me/ cfs from an infection, it kind of grew on to me. I don’t think this is the only piece to the picture for me, but it could very well be an important piece.)

 

[Violeta]

Related discussions:

Signs of Intracranial Hypertension, Hypermobility, and Craniocervical Obstructions in Patients With ME/CFS (Bragee et al., 2020)
https://forums.phoenixrising.me/thr...l-obstructions-in-patients-with-me-cfs.81446/

Neurological and spinal manifestations of the Ehlers–Danlos syndromes (Henderson et al., 2017)
https://forums.phoenixrising.me/thr...m-surrounding-peripheral-nerves-in-eds.77638/

Strange, but beta-2 adrenergic receptors have an effect on Collagen Type II.

https://journals.physiology.org/doi/full/10.1152/ajpendo.00515.2010

Here we examined β2-AR inhibition of collagen type II (Col II) expression in growth plate chondrocytes and the molecular pathways involved.

Collectively, these findings demonstrate regulation of chondrocyte differentiation through β2-AR mediated by ERK1/2 and PKA stimulation of the AP-1 factor Jun-B that inhibits the expression of Sox-6 and Col II.

 

[Pyrrhus]

Strange, but beta-2 adrenergic receptors have an effect on Collagen Type II.

https://journals.physiology.org/doi/full/10.1152/ajpendo.00515.2010

Very interesting. I would assume that this a reflection of the fact that the autonomic nervous system's general sympathetic response (fight or flight) uses β2 adrenergic receptors to redirect the body's metabolic activities from non-essential tasks, such as collagen synthesis, towards essential tasks such as supplying skeletal muscles with fuel and oxygen...

 

[Insomniac]

As a Layperson I have a few questions:

1. This test of cerebral blood flow in this paper - is it the same as the regular tilt test for dysautonomia? or is it something more invasive?

2. My blood pressure and pulse don't fit into the definition of NMH and POTS when I measure them. Yet I struggle with standing, improve with compression socks and seem to have mild symptoms of dysautonomia.

The last dysautonomia expert I went to refused to give me the tilt test because my blood pressure and pulse were not indicating it. Was he right?