Is POTS / OI / NMH another form of Deyhdration?

Dr. Briffa on dehydration:

I read a review paper recently about the assessment of dehydration. The authors conclude that we don’t have very good standardised tests for dehydration, but a reasonable test is to measure heart rate when sitting, and then again immediately on standing. During dehydration the blood volume tends to be lower and blood pressure too.

On standing, there is a tendency for blood to ‘pool’ in the lower body, causing blood pressure to drop further, which may induce a reflex increase in heart rate. If the pulse rate increases by 20 beats per minute or more on standing, this is generally taken as a sign of dehydration. However, as the authors concede, this test is not a particularly reliable way of assessing dehydration, even when blood volume is significantly depleted.

"At least two subgroups of patients with CFS can be identified by gene expression changes following exercise"

A follow up to their previous studies by "The Lights".

Gene expression alterations at baseline and following moderate exercise in patients with Chronic Fatigue Syndrome and Fibromyalgia Syndrome.
Light AR, Bateman L, Jo D, Hughen RW, Vanhaitsma TA, White AT, Light KC.

Department of Anesthesiology The Brain Institute Department of Neurobiology and Anatomy Department of Exercise and Sport Science, University of Utah, Salt Lake City, UT 84132, USA.

Abstract

OBJECTIVES:

To determine mRNA expression differences in genes involved in signalling and modulating sensory fatigue, and muscle pain in patients with chronic fatigue syndrome (CFS) and fibromyalgia syndrome (FM) at baseline, and following moderate exercise.

DESIGN:

Forty-eight patients with CFS only, or CFS with comorbid FM, 18 patients with FM that did not meet criteria for CFS, and 49 healthy controls underwent moderate exercise (25 min at 70% maximum age-predicted heart rate).

Visual-analogue measures of fatigue and pain were taken before, during and after exercise. Blood samples were taken before and 0.5, 8, 24 and 48 h after exercise.

Leucocytes were immediately isolated from blood, number coded for blind processing and analyses and flash frozen.

Using real-time, quantitative PCR, the amount of mRNA for 13 genes (relative to control genes) involved in sensory, adrenergic and immune functions was compared between groups at baseline and following exercise.

Changes in amounts of mRNA were correlated with behavioural measures and functional clinical assessments.

RESULTS:

No gene expression changes occurred following exercise in controls.

In 71% of patients with CFS, moderate exercise increased most sensory and adrenergic receptor's and one cytokine gene's transcription for 48 h.

These postexercise increases correlated with behavioural measures of fatigue and pain. In contrast, for the other 29% of patients with CFS, adrenergic α-2A receptor's transcription was decreased at all time-points after exercise; other genes were not altered.

History of orthostatic intolerance was significantly more common in the α-2A decrease subgroup.

FM-only patients showed no postexercise alterations in gene expression, but their pre-exercise baseline mRNA for two sensory ion channels and one cytokine were significantly higher than controls.

CONCLUSIONS:

At least two subgroups of patients with CFS can be identified by gene expression changes following exercise.

The larger subgroup showed increases in mRNA for sensory and adrenergic receptors and a cytokine.

The smaller subgroup contained most of the patients with CFS with orthostatic intolerance, showed no postexercise increases in any gene and was defined by decreases in mRNA for α-2A.

FM-only patients can be identified by baseline increases in three genes.

Postexercise increases for four genes meet published criteria as an objective biomarker for CFS and could be useful in guiding treatment selection for different subgroups.

ME/CFS and Peripheral Pulse as a diagnostic tool

"Our research study explored how we might use the properties of the peripheral pulse as a diagnostic tool for CFS," said Julia Newton, an honorary consultant physician at the Newcastle upon Tyne Hospitals NHS Foundation Trust and within Newcastle University's Institute for Ageing and Health. "Pulse wave abnormalities were observed in CFS and represent a potential objective measure to help differentiate between CFS patients and healthy controls."
…

"The normal homeostatic response to standing is to preserve the brain at all costs," explained Newton. "The body therefore aims to do what it can to get the blood back to the brain against gravity by increasing the heart rate and constricting the peripheral blood vessels. Our study focused on measuring and assessing pulses from multiple peripheral sites simultaneously in both CFS patients and controls in response to a posture change."
…

"With each heartbeat, the blood volume changes in the vascular bed of the tissue and the amount of light shone onto the skin by the probes varies in synchrony with this, giving a clear pulse with each heart beat," explained John Allen, a clinical scientist from the Regional Medical Physics Department of Newcastle's Freeman Hospital. "The pulse waveform has many features in terms of its size, shape and the time for it to get from the heart to the periphery as well as beat-by-beat variability. We used special computer analysis techniques to extract various pulse features and compared these to data from normal subjects to provide the diagnostic information."
…

"Further research applied to a larger number of subjects should help decide the most reliable combination of pulse features to measure so that the technique can be applied to a general population for screening of CFS with full confidence."

(via CO-CURE)

Chronic fatigue syndrome and impaired peripheral pulse characteristics on orthostasis–a new potential diagnostic biomarker

John Allen, Alan Murray, Costanzo Di Maria and Julia L Newton

Abstract

Autonomic nervous system dysfunction is frequently reported in chronic fatigue syndrome (CFS) with orthostatic intolerance, a common symptom that can be objectively assessed.

The frequent finding of autonomic dysfunction and symptoms on standing has the potential to provide a diagnostic biomarker in chronic fatigue.

In this study we explored the clinical value of non-invasive optical multi-site photoplethysmography (PPG) technology to assess cardiovascular responses to standing.

Multi-site PPG pulses were collected from tissue pads of the ears, fingers and toes of 14 patients with CFS and 14 age-matched sedentary subjects using a measurement protocol of a 10 min baseline (subject supine) followed by 3 min of tilting on a tilt table (head-up to 70°).

Percentage change in pulse timing (pulse transit time, PTTf) and pulse amplitude (AMP) at each site were calculated using beat-to-beat pulse wave analysis.

A significant reduction in the overall pulse timing response to controlled standing was found for the CFS group (using summed absolute percentage change in PTTf for ear, finger and toe sites, median change of 26% for CFS and 37% for control with p = 0.002).

There were no significant differences between subject groups for the AMP measure at any site.

Changes in AMP with tilt were, however, weakly significantly and negatively correlated with fatigue severity (p < 0.05).

Receiver operating characteristic (ROC) analysis of timing measures produced an area under the curve of 0.81.

Experimental linear discriminant classification analysis comparing both timing and amplitude measures produced an overall diagnostic accuracy of 82%.

Pulse wave abnormalities have been observed in CFS and represent a potential objective measure to help differentiate between CFS patients and healthy controls.

14 patients and 14 controls? Could be a bit more. But they choose sedentary controls, which is good.

PDF available here.

The Adenosine 2A Receptor, ME/CFS, POTS and why Caffeine can help

Adenosine normally hits receptors (2A is the important one for today) and promotes sleepiness. Caffeine, however, is an adenosine receptor ANTAGONIST, which means that it hits those same receptors in place of adenosine, and promotes wakefulness instead.
(via)

See for reference

In both ME/CFS and FMS there is a 40% subgroup, that has a Ad2A (vasoconstriction) decrease. That gene is responsible for preventing orthostatic intolerance (OI / POTS). 70% patients with this gene expression profile have orthostatic intolerance, and 20% without have POTS (it might depend when and how you measure POTS). 

and

As with the A1, the A2A receptors are believed to play a role in regulating myocardial oxygen consumption and coronary blood flow.

In addition, A2A receptor can negatively regulate overreactive immune cells, thereby protecting tissues from collateral inflammatory damage.

The A2A receptor is responsible for regulating myocardial blood flow by vasodilating the coronary arteries, which increases blood flow to the myocardium, but may lead to hypotension. Just as in A1 receptors, this normally serves as a protective mechanism, but may be destructive in altered cardiac function.

The A2A receptor is also expressed in the brain, where it has important roles in the regulation of glutamate and dopamine release, making it a potential therapeutic target for the treatment of conditions such as insomnia, pain, depression, drug addiction and Parkinson's disease.

Cerebral blood flow velocity not involved in POTS neurocognitive impairment

Increasing orthostatic stress impairs neurocognitive functioning in chronic fatigue syndrome with postural tachycardia syndrome.
Ocon AJ, Messer ZR, Medow MS, Stewart JM.

Abstract
CFS (chronic fatigue syndrome) is commonly co-morbid with POTS (postural tachycardia syndrome).

Individuals with CFS/POTS experience unrelenting fatigue, tachycardia during orthostatic stress and ill-defined neurocognitive impairment, often described as 'mental fog'.

We hypothesized that orthostatic stress causes neurocognitive impairment in CFS/POTS related to decreased CBFV (cerebral blood flow velocity).

A total of 16 CFS/POTS and 20 control subjects underwent graded tilt table testing (at 0, 15, 30, 45, 60 and 75°) with continuous cardiovascular, cerebrovascular, and respiratory monitoring and neurocognitive testing using an n-back task at each angle.

The n-back task tests working memory, concentration, attention and information processing.

The n-back task imposes increasing cognitive challenge with escalating (0-, 1-, 2-, 3- and 4-back) difficulty levels.

Subject dropout due to orthostatic presyncope at each angle was similar between groups.

There were no n-back accuracy or RT (reaction time) differences between groups while supine.

CFS/POTS subjects responded less correctly during the n-back task test and had greater nRT (normalized RT) at 45, 60 and 75°.

Furthermore, at 75° CFS/POTS subjects responded less correctly and had greater nRT than controls during the 2-, 3- and 4-back tests.

Changes in CBFV (cerebral blood flow velocity) were not different between the groups and were not associated with n-back task test scores.

Thus we conclude that increasing orthostatic stress combined with a cognitive challenge impairs the neurocognitive abilities of working memory, accuracy and information processing in CFS/POTS, but that this is not related to changes in CBFV.

Individuals with CFS/POTS should be aware that orthostatic stress may impair their neurocognitive abilities.

Alas, the sample size is a bit smallish…

(via ProHealth)

When Sinusitis isn't Sinusitis

The "problems with my nose", which I thought of as sinusitis, might not be sinusitis after all. First of all, what is Sinusitis?

Sinusitis is inflammation of the paranasal sinuses, which may be due to infection, allergy, or autoimmune issues.

So the definition is inflammation. While I don't want to rule out that inflammation is involved, I think whether I can breath freely through my nose or not has actually something to do with vasoconstriction (and blood pressure). Especially since I have been taking Equilibrant I tend to have a free nose while I lie down and start to get a blocked nose when I stand up.

Alan Light 2011 Lecture: Gene Expression Biomarkers for Chronic Fatigue & Fibromyalgia Syndromes

As a follow-up to the last post, here is his 2011 lecture (about 1 hour) by Alan Light for OFFER Utah about his very excellent ME/CFS gene-expression study.

This is objective data that there is biological reason for the symptoms [in ME/CFS and Fibromyalgia].

You may want to switch to 1080p HD to best view the slides.
(Part 1 Part 2 Part 3 Part 4 Part 5)

My take-home messages:

1. 70% of ME/CFS patients have Fibromyalgia (FMS) symptoms. And Fibromyalgia gets worse after exercise, even if the definition for FMS does not specify for it. And a majority of FMS patients (but not all) have ME/CFS symptoms.

2. TRPV1 contributes to the body's temperature set point.

3. Alan Light found a sensory definition of fatigue (The nerves at the muscle tell the brain "You are tired") in ME/CFS that contributes to the desire to use the muscles less. It is related to "actual" muscle fatigue ("The muscle is about to fail"), but it is not the same.

4. In both ME/CFS and FMS there is a 40% subgroup, that has a Ad2A (vasoconstriction) decrease. That gene is responsible for preventing orthostatic intolerance (OI / POTS). 70% patients with this gene expression profile have orthostatic intolerance, and 20% without have POTS (it might depend when and how you measure POTS).

5. FMS without CFS patients look like controls after execercise, but have different baseline levels. P2X4, TRPV1 and IL10 are expressed higher at baseline.

6. Gene expression as biomarker for ME/CFS and Fibromyalgia? Specificity 94% (6% of false negatives) and sensitivity of 65% (35% of false positives), good but not excellent biomarker, could be improved. Might be clinically available within 2 to 3 years.

7. The orthostatic subgroup should be treated differently.

8. Pregabalin or Gabapentin decrease the level of pain and of mental fatigue - maybe.

9. The cause could be increase of sensitivity of fatigue and pain, or dysfunction of the sympathetic nervous system.
(My comment, this the only flaw of Alan Light's work I can think of. He is leaving out one possibility: Of course it could be that there is an actual increase of fatigue and pain due to a pathologically increased muscle exhaustion in ME/CFS and FMS patients. If the nerves are sensing something, it could actually be there – doh!)

10. This is objective data that there is biological reason for the symptoms.
(Translated to English: "The psychosomatic school can go and f*ck themselves.")

As an addendum:
Don't miss Christopher Snell's 2012 lecture, which ties in nicely!