+100%-

Baraniuk believes chronic fatigue syndrome (ME/CFS), fibromyalgia and Gulf War Illness are  related. In fact, he calls the post-exertional malaise found in chronic fatigue syndrome (ME/CFS) a “unique characteristic of CFS that is shared by Gulf War Illness (GWI) subjects”.

Both diseases often involve a triggering event that’s caused long-term disability. The impact the Gulf War had on many of veterans of that war is astonishing. Baraniuk reports that 25 years after the first Gulf War that from @25-30% of those who participated experience PEM (exertional exhaustion), pain, migraines, gastrointestinal distress and other medical problems. Symptomatically Gulf War vets appear much like people with chronic fatigue syndrome (ME/CFS) but some important caveats exist.

GWS - me-cfs

A similar symptom presentation occurs in both ME/CFS and GWI. Depression on the other hand is more distinct. From Baraniuk

The vast majority of ill Gulf War vets are men who were subjected to a variety of toxic exposures and vaccinations not usually experienced by people with ME/CFS. In his paper “Exercise – induced changes in
cerebrospinal fluid miRNAs in
Gulf War Illness, Chronic Fatigue
Syndrome and sedentary control
subjects“, Baraniuk suggests that that one logical hypothesis regarding GWI involves lesions produced by acute acetylcholine neurotoxicity caused by people with genetically reduced levels of acetylcholinesterase activity being exposed to cholinesterase inhibitors . No such hypothesis to my knowledge has ever been proposed for chronic fatigue syndrome (ME/CFS).

Despite their symptomatic similarities, the two diseases have very different triggers and likely have different pathophysiology’s.  It gets more complex though. Baraniuk, a very creative researcher, used exercise followed by a standing test to identify two subsets of GWI patients. One called the START group (Stress Test Activated Reversible Tachycardia) responds to exercise by temporarily meeting the criteria for POTS, and  altered brain functioning including reduced brain stem volumes. The other group called STOP (Stress Test Originated Phantom Perception) developed a pattern of basal ganglia and insula activation similar to that seen in phantom pain.

Baraniuk sampled the cerebrospinal fluid of the three illness groups (START, STOP and ME/CFS) and the sedentary healthy controls before and after exercise. He looked at the miRNA patterns in an attempt to determine changes in central nervous system functioning that have occurred over time. miRNA or epigenetic studies analyze the changes in small amounts of RNA which we accumulate over time in response to events. Because these small RNA’s are capable of turning on or off genes they’re a prime candidate in any disease which gets triggered by some event.

This is first study that I know of that’s examined cerebrospinal fluid factors before and after exercise in ME/CFS.

Results

“We clearly see three different patterns in the brain’s production of these molecules in the CFS group and the two GWI phenotypes. This news will be well received by patients who suffer from these disorders who are misdiagnosed and instead may be treated for depression or other mental disorders.” Baraniuk.

Baraniuk’s decision to introduce an exercise stressor paid off when, as we’ve seen at times in ME/CFS, all the groups showed no difference at all in their  miRNA profiles at rest. After exercise, things changed, and they changed most dramatically for the ME/CFS group.

Reduced levels of three miRNA’s (miR-let-7i-5p, miR-93-3p, miR-200a-5) after exercise in the ME/CFS and GWS groups but not the healthy controls suggested some degree of commonality was present in the illness groups.  Decreased expression of MiR-let-7i in a rat model of depression suggested that decreased levels of this miRNA might contribute to the mood alterations  sometimes seen post-exercise in ME/CFS and GWS.

Chronic Fatigue Syndrome (ME/CFS) Group Stands Out

After exercise the 12 reduced miRNA’s in ME/CFS patients clearly differentiated them from people with GWI. ME/CFS was the only group to display no elevation in miRNA levels after exercise. (Five elevated miRNAs occurred in the sedentary controls, 3 in the START group and 1 in the STOPP group.) One miRNA found reduced in ME/CFS might be associated with pre-mature aging, another with Alzheimer’s and amyloid deposition, another with the leakage of inflammatory factors into the brain, and another with increased cell suicide in the brain.

Aging – Past studies suggested that the findings could make sense. Premature aging, for instance, may be taking place in ME/CFS and /or fibromyalgia. The CDC reported that telomere length – believed to reflect aging – was significantly shorter in ME/CFS patients. Telomere length also trended lower in fibromyalgia patients than healthy controls, and was associated with increased pain in that disease. FM patients scored about 20 years older than expected in cognitive testing. Reduced heart rate variability – found in both ME/CFS and FM – occurs as we get older as well.

(On a side note a study suggesting that age does make a difference in ME/CFS found that older people with ME/CFS experience more fatigue and depression and greater autonomic dysfunction (reduced parasympathetic/increased sympathetic functioning – i.e. reduced heart rate variability) than younger people.)

Dementia –  No studies that I know of have examined the risk of dementia in ME/CFS but a recent fibromyalgia study suggested that an increased risk for dementia/Alzheimer’s may exist in fibromyalgia. (Despite the increased risk, the odds of getting dementia were still quite low). While  Baraniuk noted that the miRNA patterns found in ME/CFS were different from those found in Alzheimer’s disease, one reduced miRNA in ME/CFS called miR-19b-3p was lower in both the cerebral spinal fluid and serum of Alzheimer’s patients as well.

.org/blog/2017/10/05/fibromyalgia-fibro-fog-dementia-cognition/

Baraniuk didn’t mention it but his small 2005 cerebral spinal proteome study suggested increased amyloid levels could be present in ME/CFS as well. In an interview Baraniuk proposed that the aggregation of amyloid proteins in the blood vessels of ME/CFS patients could be causing small amounts of bleeding in their brains and questioned whether the location of those small blood vessel ruptures might determine whether one has ME/CFS or FM or GWI.  Baraniuk speculated that  these proteins might interfering with the brains ability to control the autonomic nervous system.

blood vessels brain ME-CFS

A past study suggested that damage to the blood vessels in the brain might be occurring in ME/CFS

Blood-Brain Barrier –  Nath has suggested that immune cell migration into the brain could be causing neuroinflammation in ME/CFS, and, in fact, the integrity of the blood-cerebrospinal fluid barrier ended up being a major topic in this paper. A finding of increased cell suicide in the brain after exercise might not be such a surprise if exercise is inducing inflammation. Cook has shown that cognition and brain functioning are altered one day after exercise in ME/CFS.

Caveats – Baraniuk mentioned some caveats to miRNA analysis of cerebral spinal fluid (CSF) including the “remarkable lack of consensus” regarding the levels of miRNA expected found in healthy controls. (Baraniuk noted that he used more CSF fluid than some other studies. ) Note that information on the functions of many of the reduced miRNA’s in ME/CFS is lacking, and the information on those that were found can be pretty sketchy; i.e. based on one or two, sometimes non-human studies. This issue of data acquisition out lapping our understanding of what it means is pretty common in “omics” studies.

Baraniuk has been exploring how exercise effects the brains of ME/CFS/GWS patients for years. His small 2013 study linking increased lactate levels in a subset of GWI patients to reduced exercise capacity was intriguing giving the high lactate levels Shungu has found in ME/CFS.  As noted above, another exercise study uncovered two subsets of GWI patients: one developed increased pain after exercise and another temporarily developed POTS and exhibited signs of brainstem and basal ganglia problems.

The Baraniuk lab at Georgetown University in Washington D.C. is currently recruiting for ME/CFS patients for an NIH funded two-day exercise/MRI study.

Conclusion

Some researchers believe ME/CFS occurs when genetics we are born with collides with some environmental factor – an infection or toxin or other stressor. Studies indicate that anything which substantially stresses the body  (infection, birthing procedures, adverse childhood events) can set up people for disease in later life.  If that scenario is true then miRNA’s -the  substances which turn on and off genes in response to different events-  are prime culprits in the search for the cause of ME/CFS and GWI..

Despite the similarity in symptoms, Baraniuk’s study of cerebral spinal fluid miRNA’s suggests that the central nervous systems of ME/CFS and GWI patients may respond very differently to exercise.  The results need to be validated and interpreting them can be difficult given our limited knowledge of the effects that individual miRNA’s have, but they suggest, that too much exercise might harm the integrity of the blood-brain barrier, or alter cognitive functioning (studies indicate that’s true), interfere with cell suicide, or exacerbate an early aging process in ME/CFS.

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