Today, Thursday 15 Oct: Solve webinar with Dr Alan Light: New Developments in ME/CFS Research

[lansbergen]

Can anyone explain why that is not the case?

Not me but when I was very severe my heart seemed to stop several times and then I could feel it fill and starting pumping again. Has not happend in a long time now but it was scaring when it happened.

 

[Gijs]

In the Netherlands there is cardiologist who found a significant drop in bloodflow (20 till 40%!) through the brain when a patiënt is sitting and standing compared to lying down and healthy people. I wonder in POTS if it has something to do with compensation for low bloodvolume or a problem in the peripheral system.

 

[Gijs]

Not me but when I was very severe my heart seemed to stop several times and then I could feel it fill and starting pumping again. Has not happend in a long time now but it was scaring when it happened.

This is diastolic dysfunction.

 

[Sidereal]

That might have been due to time limitations ... he had 45 minutes to cover a lot of ground, and OI was a bit peripheral.

Agreed, and I wasn't criticising him for not going into detail, I was just explaining what the reality is re: blood pressure in POTS. I think what he was trying to say is that POTS is not orthostatic hypotension.

 

[Bob]

I've found gabapentin useful for the immediate relief of the symptoms of my new type of ME esp for relieving pain and reducing (what feels like) joint inflammation. It relieved the pain immediately, and reduced the inflammation immediately. Unfortunately the side effects were intolerably severe, so I had to stop it after a week.

 

[Sidereal]

In the Netherlands there is cardiologist who found a significant drop in bloodflow (20 till 40%!) through the brain when a patiënt is sitting and standing compared to lying down and healthy people. I wonder in POTS if it has something to do with compensation for low bloodvolume or a problem in the peripheral system.

Before the term POTS even existed people had noticed the existence of a curious syndrome termed "idiopathic hypovolemia" ( = low blood volume of unknown cause) where people had low blood volume, orthostatic tachycardia and labile blood pressure.

For example:

Ann Intern Med. 1986 Mar;104(3):298-303.
Idiopathic hypovolemia.
Fouad FM, Tadena-Thome L, Bravo EL, Tarazi RC.
Abstract
Eleven patients with orthostatic intolerance had, for no detectable reason, a marked reduction in blood volume (73 +/- 2.29% [SE] of normal). Head-up tilt caused a pronounced increase in heart rate (+ 39 +/- 6 beats/min); one patient had a vasovagal episode after the initial tachycardia. Extensive diagnostic study excluded pheochromocytoma, hypoaldosteronism, or any obvious cause for hypovolemia (total plasma catecholamines, 372 +/- 53 ng/L; plasma aldosterone level, 14.5 +/- 2.56 ng/100 mL; plasma cortisol level, 18.5 +/- 2.4 ng/100 mL). The supine hemodynamic pattern (decreased cardiac output and increased total peripheral resistance with normal ejection fraction and mean transit time) was markedly different from that of hyperbeta adrenergic states. Acute plasma volume expansion (+ 11 +/- 2%) in ten patients using human serum albumin improved both their symptoms and heart rate response to tilt. After long-term blood volume expansion with florinef (E.R. Squibb, Princeton, New Jersey), 0.1 mg twice a day, and a high-salt diet, the head-up tilt test was repeated in five patients. The response was normal in four patients. These observations outline a syndrome of marked idiopathic hypovolemia with symptomatic labile hypertension and intolerance to head-up tilt, alleviated by volume expansion.

Standing up of course worsens the hypovolemia in the upper part of your body including the brain, making all symptoms worse. There is a reason why so many ME patients are forced to lie down or recline with their feet up all day, and it's not because they are simply "fatigued". A person who is fatigued would get better by sitting down to rest whereas in these people sitting down does not alleviate the symptoms driven by autonomic dysfunction, only lying down flat or reclining with elevated feet does.

 

[Jonathan Edwards]

What he said about POTS and blood pressure being normal or high is oversimplified. In POTS you often have rising diastolic when standing, with systolic staying the same or even dropping, resulting in a narrowing of pulse pressure and feeling pre-syncopal.

If diastolic rises then the heart would seem to be doing all that it should in the way of pumping so that does not seem to address my concern. I am genuinely interested in an explanation for this but I do not think that will cover it.

 

[Hutan]

Light talks of an 85% homology in an epitope.

Yes, I thought that 85% didn't sound so great. And your point about that 85% concordance being only the amino acid sequence is a very good one - by the time it's all folded up the quaternary structure could be very different.

But in POTS it is said that the pressure is normal or high.

I'm not sure about the answer to your POTS question. But people with POTS typically (although not always) have low (rather than high)blood pressure. Upon standing, the blood pressure typically stays the same or increases, but from a low base.

[sorry, was unaware of all the subsequent discussion when I posted this]

 

[Bob]

Ignoring the 85% homology in an epitope issue for the moment. Even if a virus can be a direct cause of autoantibodies, via molecular mimicry, i'm sceptical about strep (or any other virus) being the direct cause of autoantibodies in a majority of ME patients because I don't believe that ME is related to a single common virus. A wide variety of viruses and other stressors seem to be related to ME.

To find answers, I think we've got to be more imaginative than to believe that EBV, herpes or strep etc., cause ME, unless they all disrupt the immune system for the same reason. In which case we've got to look at that underlying mechanism that goes wrong when ME is triggered.

 

[Gijs]

Even if a virus can be a direct cause of autoantibodies, via molecular mimicry, i'm sceptical about strep being the direct cause of autoantibodies in a majority of ME patients because I don't believe that ME is related to a single common virus. Many different viruses and other stressors seem to be related to ME.

To find answers, I think we've got to be more imaginative than to believe that EBV, herpes or strep etc., cause ME, unless they all disrupt the immune system for the same reason. In which case we've got to look at that underlying mechanism that goes wrong when ME is triggered.

NK cel dysfunction can explain replication of viruses like EBV, i believe EBV and herpesviruses playing a major rol in ME. I agree there is some type of mechanisme responsable.

 

[Sidereal]

If diastolic rises then the heart would seem to be doing all that it should in the way of pumping so that does not seem to address my concern. I am genuinely interested in an explanation for this but I do not think that will cover it.

Well, you cannot look at the diastolic in isolation. If you want to get an idea of someone's stroke volume, you look at the difference between systolic and diastolic (i.e. pulse pressure). In POTS patients you will often see a horrible pulse pressure like 20 or 25 when upright for a while (or, in severe cases, immediately upon standing or even sitting).

 

[Valentijn]

If diastolic rises then the heart would seem to be doing all that it should in the way of pumping so that does not seem to address my concern. I am genuinely interested in an explanation for this but I do not think that will cover it.

If diastolic rises, but systolic remains the same or even drops, then the pulse pressure (difference between the two) drops. Since pulse pressure indicates the volume of blood being pumped with each beat, having this go to 50% of normal is probably causing problems.

Normal pulse pressure is about 40-50. When due to sudden blood loss, pulse pressure under 25 is considered a medical emergency. ME patients here frequently report pulse pressure regularly falling under 25 and even under 20, though it then gets hard to measure due to the weakness of the pulse.

For me, my pulse pressure would get under 25 on a daily basis when I was unmedicated with Strattera or Yohimbe. Usually it would start out okay (30-35) in the morning, then drop throughout the day. Standing for a while would also cause it drop, sometimes after 30 minutes, sometimes faster.

At that point my oxygen saturation starts to fall, and that is when tachycardia kicks in. Once the tachycardia starts, my oxygen goes up to 98/99, my heart rate slows a bit, oxygen dips down to 94/95, and tachycardia starts again until my oxygen saturation rises. This cycle can go on for hours when I've recently over-exerted myself, or am in the midst of a crash, even with medication. It will continue to happen even when lying down during a bad episode, though it does help a little.

 

[Sidereal]

Once the tachycardia starts, my oxygen goes up to 98/99, my heart rate slows a bit, oxygen dips down to 94/95, and tachycardia starts again until my oxygen saturation rises.

Which to my mind suggests that the tachycardia seen in ME is not something that should just be artificially knocked down with beta blockers because you may actually be interfering with the body's attempt to maintain adequate cardiac output in the face of low stroke volume.

 

[Bob]

I think the observations of gene expression with and without the drugs (pregabalin/gabapentin), in relation to symptom severity, is very interesting if it is replicable, because it's a very strong indicator of the biomedical nature of the disease. i.e. demonstrating that a drug that normalises gene expression reduces symptoms accordingly. I don't know what genes they are; he says they relate to fatigue. As with all his work, it's the polar opposite of false illness beliefs and maladaptive avoidant behaviour.

 

[Valentijn]

Which to my mind suggests that the tachycardia seen in ME is not something that should just be artificially knocked down with beta blockers because you may actually be interfering with the body's attempt to maintain adequate cardiac output in the face of low stroke volume.

Agreed. Certain triggers for tachycardia definitely need to be ruled out before any direct attempt to reduce the tachycardia itself

 

[Hutan]

I have been tracking my heart rate(HR) and blood pressure(BP) morning and night, supine and standing for a few months now. I noticed that when I had migraines and took ibuprofen, HR and BP normalised (no or less tachycardia upon standing, no low pulse pressure, shock index (systolic/HR) of less than 1). So I took ibuprofen when not having a migraine and the same improvement occurred.

I have now been on mobic (another NSAID) for nearly a week and it seems to have the same effect. i.e. normalising HR and BP.

So, in my case I think controlling inflammation may reduce the orthostatic intolerance (and possibly other symptoms).

 

[Jonathan Edwards]

If diastolic rises, but systolic remains the same or even drops, then the pulse pressure (difference between the two) drops. Since pulse pressure indicates the volume of blood being pumped with each beat, having this go to 50% of normal is probably causing problems.

Normal pulse pressure is about 40-50. When due to sudden blood loss, pulse pressure under 25 is considered a medical emergency. ME patients here frequently report pulse pressure regularly falling under 25 and even under 20, though it then gets hard to measure due to the weakness of the pulse.

For me, my pulse pressure would get under 25 on a daily basis when I was unmedicated with Strattera or Yohimbe. Usually it would start out okay (30-35) in the morning, then drop throughout the day. Standing for a while would also cause it drop, sometimes after 30 minutes, sometimes faster.

At that point my oxygen saturation starts to fall, and that is when tachycardia kicks in. Once the tachycardia starts, my oxygen goes up to 98/99, my heart rate slows a bit, oxygen dips down to 94/95, and tachycardia starts again until my oxygen saturation rises. This cycle can go on for hours when I've recently over-exerted myself, or am in the midst of a crash, even with medication. It will continue to happen even when lying down during a bad episode, though it does help a little.

Now I am even more unclear what is supposed to be going on. Light is suggesting that the tachycardia causes poor tissue perfusion because the heart beats too fast to be efficient. You are suggesting that the tachycardia increases perfusion and oxygenation. I get the impression that everyone is agreeing that at least Light has got this wrong in terms of blaming poor perfusion on tachycardia.

My understanding is that to get a dip in cardiac output with tachycardia you have to at least double heart rate - say from 80 to 160, although maybe not in a very pathological heart like in HOCM. If you double heart rate you can get the same cardiac output with a 50% reduction in stroke volume, which I think is almost certainly going to be associated with some reduction in pulse pressure simply because the run off time is halved.

But neither stroke volume nor even cardiac output are the physiological end point anyway. They are means to an end rather than the end, which is adequate perfusion pressure at arteriolar level. That I think has to be predominantly determined by diastolic pressure in the sense that if the peripheral arteriolar bed was not being filled diastolic pressure would have to go down. If not, at least it will be determined by mean pressure and the claim I see everywhere is that in POTS the mean pressure does not fall - the pulse pressure argument becomes non-sequitur here.

Clearly, the tissues may be ischaemic if there is peripheral arteriolar constriction - as would occur in all but the late stages of shock. But then the problem is not the tachycardia, it is the peripheral constriction, presumably in combination with something that limits cardiac output on the filling side such as low central venous pressure or input valve stenosis (which obviously would not occur intermittently except in the rare case of atrial myxoma).

Which seems to bring us back to the idea that the tachycardia is probably a reaction to low central venous pressure on standing. Which would tend to put the problem not with vasomotor receptors (unless in the great veins) but more with volume control in the kidney.

 

[Marco]

Dr Light then tied all of that into his previous work showing altered expression of the adrenergic alpha 2A receptor in ME patients following exertion, compared to controls. And from there he went into some newer placebo-controlled research regarding Lyrica in ME/CFS + FM and pure FM patients versus controls.

Basically about half of the FM patients on placebo, with or without CFS, had expression of about 6 genes before and after exertion (several time points) which was radically different to healthy controls. In those patients, Lyrica then largely (but not completely) normalized gene expression. In the other half when on placebo, they started with gene expression closer to the healthy controls, and Lyrica made things quite a bit worse.

So they potentially identified responders and non-responders to Lyrica, and their report of improved or worsened symptoms on Lyrica corresponded with their gene expression when on Lyrica. So basically if Lyrica made them feel awful, it was because Lyrica was altering things in a pretty unhelpful manner.

Just picking up on this, and it may be in no way significant, but these findings remind me of the large Japanese sensory gating study that found two distinct CFS subgroups - one over-responsive to stimuli and the other under-responsive.

 

[Valentijn]

Now I am even more unclear what is supposed to be going on. Light is suggesting that the tachycardia causes poor tissue perfusion because the heart beats too fast to be efficient. You are suggesting that the tachycardia increases perfusion and oxygenation. I get the impression that everyone is agreeing that at least Light has got this wrong in terms of blaming poor perfusion on tachycardia.

He was talking about POTS, which should be tachycardia which isn't being triggered by a different blood pressure issue. But POTS is usually just found in a minority of ME patients, whereas most will have something a bit more subtle, such as Neurally Mediated Hypotension (NMH). I have something which probably fits under NMH, and my tachycardia is purely reactive and probably helpful in compensating for my narrow pulse pressure.

But other ME patients have tachycardia despite normal or high blood pressure and/or pulse pressure. So his bit about POTS seemed to be suggesting an explanation for why tachycardia feels so awful and/or similar to low blood pressure or low pulse pressure, even when pulse pressure and blood pressure are not low.

 

[Sidereal]

I have been tracking my heart rate(HR) and blood pressure(BP) morning and night, supine and standing for a few months now. I noticed that when I had migraines and took ibuprofen, HR and BP normalised (no or less tachycardia upon standing, no low pulse pressure, shock index (systolic/HR) of less than 1). So I took ibuprofen when not having a migraine and the same improvement occurred.

I have now been on mobic (another NSAID) for nearly a week and it seems to have the same effect. i.e. normalising HR and BP.

So, in my case I think controlling inflammation may reduce the orthostatic intolerance (and possibly other symptoms).

How are your other ME symptoms while your HR and BP are normal?