The 24th International Symposium on the Autonomic Nervous System was chock full of potential insights for people with chronic fatigue syndrome. We used Dysautonomia International’s excellent overview of the relevant studies as a starting point. (Thanks to Issie for alerting me to the overview.)
Is the autonomic nervous system going to be ground zero for chronic fatigue syndrome and fibromyalgia? This overview suggests, at the very least, it’s going to be a major factor.
Dysautonomia / Dysauto – “immunomia” – The Autoimmune Connections to Dysautonomia Grow
The autoimmune connection in dysautonomia (autonomic nervous system disorders) and the autonomic nervous system connection in autoimmune disorders are growing.
Postural Orthostatic Tachycardia Syndrome (POTS)
A study suggested that POTS, a disorder associated with ME/CFS, may be an autoimmune disorder as well. Starting off their abstract by noting that POTS is often triggered by a viral infection, these Oklahoma and Vanderbilt University researchers reported that their small study (14 POTS patients) found increased alpha- and beta-adrenergic receptor activity that they were able to stop by using an alpha-adrenergic receptor blocker.
The POTS patients had elevated levels of a1AR autoantibodies and some had beta-adrenergic antibodies. The high levels of the a1AR antibodies suggested POTS patients had to produce more norepinephrine and increase their heart rates more rapidly; i.e. they had to put their sympathetic nervous system in overdrive in order to get blood out to the tissues.
The Lights’s finding of increased gene expression of all alpha– and beta-adrenergic receptors in ME/CFS compared to controls after exercise suggested that these pivotal blood vessel components were disturbed in both disorders.
The authors believe their ﬁndings provide “strong support for an autoimmune basis for the increased upright plasma norepinephrine and excessive tachycardia observed in POTS patients.”
Taking a look at few other disorders, we can see a growing autonomic nervous system/autoimmune connection and some serious overlap with chronic fatigue syndrome.
Primary Biliary Cirrhosis
We know that Dr. Julia Newton is engaged in a Rituximab trial in primary biliary cirrhosis (PBC), an autoimmune disorder with high rates of fatigue as well as autonomic issues. The overlap between this autoimmune disease and chronic fatigue syndrome in astonishing. Similar muscle pH problems occur in both PBC and ME/CFS. Newton has stated that PBC has exactly the same cardiac energetics and similar autonomic nervous system dynamics as ME/CFS. Both feature reduced heart rate variability. Autonomic and sensory nerve fiber neuropathy is common in PBC and may be common in ME/CFS and FM.
Newton appears to have found the same type of increased ‘cerebrovascular resistance’ — which I believe refers to narrowed blood vessels — in PBC as is found in POTS and ME/CFS (see below}. Newton recently proposed that people with PBC show accelerated cardiac ‘aging’. She believes the autonomic nervous system problems in PBC may simply be an attempt to compensate for deficiencies elsewhere (as do some ME/CFS and POTS researchers).
Primary biliary cirrhosis has been known to be an autoimmune disease since the 1970s. However, only in the last 6 years or so, largely due to Dr. Newton’s efforts, has anyone looked at the autonomic nervous system. Dr. Newton appears to have locked onto PBC because of the enormous fatigue issues which she believes may be the result of autonomic nervous system dysfunction. Dr. Newton has begun the same process, and has been getting similar results, in Sjogren’s Syndrome, another autoimmune disorder. It took researchers about 50 years to glom onto Sjogren’s Syndrome’s autonomic nervous system issues.
Complex Regional Pain Syndrome
On the flip side, we know that studies suggest that CRPS, which is chockfull of autonomic nervous system issues, may end up being an autoimmune disorder as well. CRPS was described decades ago, but it only became associated with autoimmunity in the last 10 years, and only seriously associated in about the last five. It can take considerable time for researchers to begin to look for and then pin down a state of autoimmunity, and, in fact, the autoimmunity present in CRPS is atypical.
We know autonomic nervous system problems are present in ME/CFS/FM. We know that Rituximab works in subset of ME/CFS patients. Is it just a matter of time before an autoimmune disorder is documented in subset of ME/CFS patients?
Hyperadrenergic POTS – Meet Chronic Fatigue Syndrome
An astounding case of research mimicry took place when POTS researchers essentially duplicated the results of a recent UK study on ME/CFS. This POTS study found that hyperadrenergic POTS patients hyperventilate when they stand, lowering their blood CO2 levels. This causes the blood vessels in their brains to constrict reducing blood flow to the brain.
POTS patients had an immediate 30 percent reduction in cerebral blood flow upon being tilted up. Struggling to make up the deficiency, their hearts exploded into action with their heart rates almost doubling from a normal 78 bpm to 130 bpm. They at least partially succeeded, as cardiac output — driven by the intense heart rate — remained stable.
If I’m reading this correctly, the 30 percent reduction in blood flow to the brain did not occur because of blood pooling in the legs (‘no excessive regional blood volume shifts occurred’). Rather, it occurred because narrowed blood vessels reduced blood flow to the brain.
Panic Time – Muscle sympathetic nervous activity started out normal, but it increased so much during the tilt table test that the test was stopped due to MSNA-produced feelings of panic and anxiety.
Hyperventilation – The hyperventilation that ensued that caused severely low CO2 levels. Arterial blood flows to the brain via the carotid arteries were so reduced as to produce a condition called ischemic hypoxia. Ischemic hypoxia or ‘stagnant hypoxia’ occurs when slowed movement of the blood reduces oxygen delivery to the tissues even when oxygen content and saturation of the blood is normal. The ‘Bohr effect’ which decreases CO2 levels when blood pH levels drop contributed to further hypoxia. The sympathetic nervous system apparently kicked in to try to remedy the situation by increasing blood flows, but further reduced CO levels and, as we saw, induced feelings of panic.
The kicker was that giving the POTS patients carbon dioxide during the tilt test normalized the blood flows to their brains, and stopped their tachycardia (rapid heart beats) and their hyperventilation. (For some reason they did not suggest patients start breathing carbon dioxide.)
This study was more complete, but its results followed almost word for word Dr. Newton’s recent finding in a small group of chronic fatigue syndrome patients. Was she testing ME/CFS patients with hyperadrenergic POTS or were these ME/CFS patients? My guess is that they were ME/CFS patients, or maybe they were both. Or maybe it’s a moot point, and the next abstract suggests why.
Your Next Diagnosis is… POTS
In the tilt table version of an ME/CFS repeat exercise test, patients whose heart rate increased during standing but who did not meet the criteria for POTS were given another, longer, tilt test. Almost half of them ended up meeting the criteria for POTS.
This, like the repeat exercise test employed in chronic fatigue syndrome, much more accurately reflects functionality because it more reflects the stressors of every day life: getting up and down again and again, standing for long periods, etc.
This finding suggests that POTS may be much more common (and much more underdiagnosed) than previously thought, and that the diagnostic criteria should be broadened. The takeaway from this is that If you have problems standing or remaining upright, and your doctor didn’t think you have POTS, you still might.
My guess is that the more the researchers dig into the standing problem the more they’ll find, and they’re just understanding the grosser aspects of it now. Who with chronic fatigue syndrome, after all, doesn’t have some problems with standing?
The Deconditioning Theory Takes a Hit
Because deconditioning can actually cause orthostatic intolerance (OI), the question of how much deconditioning contributes to orthostatic intolerance is HUGE. One train of thought has been that a considerable number of people with ME/CFS become immobile when they become sick, and then they become orthostatically intolerant by staying in bed so much. They’re so freaked out by their symptoms at that point that they never really get up again.
The problem is that staying in bed can cause orthostatic intolerance, and this makes it difficult to determine if orthostatic intolerance is from deconditioning or from a physiological problem.
Mayo Clinic researchers believe, though, that they have a way. A Mayo Clinic study finding that markers of deconditioning are ‘only marginally associated’ with heart rate response in a group of people with OI suggested that deconditioning is “unlikely to be the primary causative factor in orthostatic intolerance.”
They acknowledged that deconditioning is rampant in orthostatic intolerance, and reported that ‘reconditioning programs’ can be very helpful. But they concluded that deconditioning itself is only marginally relevant in causing orthostatic intolerance.
I think we’re getting somewhere. I think it’s time for the NIH to pony up for a Symposium on Chronic Fatigue Syndrome/POTS/Fibromyalgia and the Autonomic Nervous System.
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