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The Muscle-Brain Connection in ME/CFS Revealed

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Reprinted with the kind permission of Cort Johnson and Health Rising.

By Cort Johnson, July 22, 2014

People with Chronic Fatigue Syndrome have weakened muscles and, let’s face it, weakened brains as well. They can’t exercise worth a darn and their ability to focus, to process information quickly and to retain it, is shall we say, blunted. One would think those two problems are not related, but a recent Belgium study suggests they are intimately related.
We recently saw Dr. Bateman incorporate a bunch of different findings into a ‘big picture’ view of ME/CFS. This studies findings suggest that was a good thing to do.

The Study

Can recovery of peripheral muscle function predict cognitive task performance in chronic fatigue syndrome with and without fibromyalgia? Ickmans K, Meeus M, De Kooning M, Lambrecht L, Pattyn N, Nijs J. Phys Ther. 2014 Apr;94(4):511-22. doi: 10.2522/ptj.20130367. Epub 2013 Dec 20.

Studies have shown that muscle recovery in Chronic Fatigue Syndrome takes longer than expected and the cognition problems (slowed information processing, reduced short term memory, difficulty concentrating) are evident.

These Belgium researchers wanted to know whether ME/CFS patients with longer muscle recovery times also did more poorly on the cognition tests. They gave cognition tests to ME/CFS and ME/CFS plus Fibromyalgia patients one day and then did a muscle challenge test using a handgrip tool the next.


They found that ME/CFS patients with or without Fibromyalgia who recovered their strength less quickly also did worse on the cognition tests; ie. poor muscle recovery is associated with reduced brain power. That’s probably not surprising to people with ME/CFS who get hit both physically and mentally after exerting themselves too much, but now it has to be explained.

The ME/CFS patients with Fibromyalgia (Wolfe criteria) also did worse on the cognition tests and took longer to recover from the muscle test than ME/CFS patients without FM. Since the more comobid conditions a person has the worse off they tend to be, this makes sense.

The Muscle Brain Connection

The authors suggested that reduced blood vessel formation could, among other things, be responsible for their findings. The Ickman’s group tied the muscle recovery/cognition results to a study by De Lange showing that reduced grey matter in the brains of ME/CFS patients was associated with reduced physical activity.

In that vein they suggested that reduced angiogenesis – blood vessel formation – and neurogenesis – nerve formation – associated with reduced physical activity might be responsible.

Indeed, it’s possible all thingsconsidered, that the more fit a person with ME/CFS is the better they do cognitively.

They also pointed to central sensitization as a probable factor; the more central sensitization present – the worsened muscle recovery and the poorer cognition you exhibit. Increased pain can dampen both muscle functioning and cognition, and the fact that the CFS patients with Fibromyalgia had substantially worse cognition than the ME/CFS patients without FM fit this idea.  
They noted that other possibilities are present and we’re going to take a look at one.

Autonomic Nervous System

“Our findings add to the growing body of evidence linking autonomic dysfunction to the symptomatology in this poorly understood disease” Beaumont  et. al.         

Other factors, however, have been associated with poor cognition. Two consequences of autonomic dysregulation; low heart rate variability (HRV) and the presence of orthostatic symptoms, have been associated with reduced cognition in ME/CFS. Australian study authors argued that vagus nerve withdrawal was best associated with cognitive problems. (Interestingly, they also found reduced heart rate ‘recovery periods’ during cognitive testing. In a big picture attempt they proposed that pre-frontal cortex damage results in loss of autonomic nervous control, reduced vagal tone and poor cognition) Could autonomic issues and reduced blood flows also play a role?

Newton’s finding that poor pH handling by the muscles in ME/CFS patients is associated with low heart rate variability effectively tied the autonomic nervous system problems  in ME/CFS  to  muscle recovery issues. Her ability to further tie reduced pH handling in the muscles to reduced blood flows to the brain directly linked muscle, brain and ANS issues together.

Newton’s studies in other disorders back up her focus. Autonomic nervous system symptoms were highly correlated with cognitive issues in a immune thrombocytopenia study. Newton proposed that impaired ‘cerebrovascular autoregulation’ (impaired  blood flows to the brain) were causing cognitive declines in primary biliary cirrhosis (PBC), another severely fatiguing disease, In 2008 Newton found that brain lesions and autonomic  issues were associated with cognitive declines in PBC.

All this is to say that reduced grey volume and angiogenesis may very well be associated with both reduced cognition and muscle recovery in ME/CFS as the authors suggest, but an increasing body of work suggests autonomic dysregulation may play a key role.

With the low blood volume and autonomic nervous system issues present in  ME/CFS it’s not  hard to envision systemically reduced blood  flows causing problems with  both muscle recovery and the cognition. We do, after all, have two aerobically active areas of the body (muscles, brain) with problems.  Perhaps it’s not so difficult to connect the two after all; simply follow the blood.

Time will tell. For now it’s great to see a connection made between these two critical problems in ME/CFS. At   some point they and all the other seemingly disaparate findings in ME/CFS need to be explained.


It’s big picture time; what could be causing issues in two seemingly different systems?

Longer muscle recovery times are associated with cognitive declines in Chronic Fatigue Syndrome (ME/CFS).  Explaining this strange muscle-brain connection works will likely require showing how similar issues affect both system. The authors propose that reduced grey matter in the brain and central sensitization may play a role. The major controller of blood flows  to both – the autonomic nervous system – is another possibility.

This study was intriguing because it connected too seemingly separate systems; the muscles and the brain.  Explaining the results will require stitching together two systems that are not ordinarily stitched together – a good exercise in  a disease that affects so many systems of the body.

About the Author:  Cort Johnson has had ME/CFS for over 30 years. The founder of Phoenix Rising and Health Rising, Cort has contributed hundreds of blogs on chronic fatigue syndrome, fibromyalgia and their allied disorders over the past 10 years. Find more of Cort’s and other bloggers’ work at Health Rising.

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9 thoughts on “The Muscle-Brain Connection in ME/CFS Revealed”

  1. AmaranthRose says:

    Interesting. I was not aware of the linkage between muscle reluctance and mental performance. I know that as my physical condition deteriorates, my mental functions are gradually getting worse, but did not equate cause with result. On days when the FM acts up, I find it harder to do tasks that require mental agility. This can be bad, as sometimes it means I don’t get my bills paid as soon as they would like to be paid, because I simply can’t handle the complexities of writing checks and mailing envelopes. This article gives me more understanding of my disease and hope for the future.

  2. ex-cfs says:

    There are other possible links. Two come to mind for me.

    1. Testosterone levels

    My 8 year probable fibromyalgia (undiagnosed at the time) went away within 24 hours after receiving a pellet implant of bio-identical testosterone. This happened after 7 months of weekly injections of synthetic testosterone.

    Testosterone builds and strengthens muscles and increases bone density. As well, it increases focus and drive in the brain. I would say that testosterone has its biggest impact in clearing my thinking and giving me drive to do anything (libido is not only in the sexual sense). In doing so, it speeded and clarified my cognitive processes.

    2. Good fats

    These might include omega 3 EFAs and phosphatdylcholine (PC) and phosphatdylserine (PS). The first is concentrated in the brain and heart, and assists muscle function. The latter two are important for brains, and may speed neurotransmission. I don’t know what, if anything, they do in muscles. But they are part of lethicin, which a lot of body builders take.

    There may be other links. It would be useful to think through all the links and test for these.

    1. not2care says:

      this is a new one for me..most people diagnosed with fibromyalgia are women…whether there’s a cultural bias or not I couldn’t say…sounds like something you could take to a knowledgeable doctor for consideration..may be that is information they can use to actually diagnose you properly…there’s nothing as frustrating as knowing you’re sick but no one in the medical profession seems to see any connection by symptoms to any known disease or syndrome..I don’t understand how low testosterone and replacement therapy would help me, a woman though…my son has been sick with fibromyalgia since he was 11 or so..so how testosterone would fit into his illness is not clear to me either…

  3. pomeranian says:

    I have CMT 2 (that is comprised on 1 and 2; a thin myelin sheath and breakages) and CFS which appears to be making its way to Fybromyalgia. DOoes anyone else have the two and is there anything to suggest that the one impacts upon the other?

  4. BeckieC says:

    I showed a positive tilt test for autonomic nervous disorder within 18 months of military “cocktail vaccines” for predeployment Desert Storm, 1990-91. More importantly, I suffer vaccine-derived infections of my heart and brain that impair aerobic exercise and memory. Cytomegalovirus (CMV) from green African monkey kidney tissue used to culture most U.S. vaccines thrives off of and damages vascular endothelium: heart wall, but not the heart muscle, lining of most vessels and veins, plus aortas (brain, heart and abdomen among all others).
    According to Genentech, manufacturer of Valcyte antiviral that controls spread of CMV, the monkey infection shuts down the human brain before stopping other major organs, including the heart.
    Research has proven that humans cannot mount an immune response to that particular monkey virus, similar to AIDS. Treatment with Valcyte is for life. Valtrex may be necessary to prevent cardiac episodes, such as Long QT Syndrome, tachycardia, female heart attacks that do not show on EKG after the fact.
    Anyone who claims their CMV has gone into remission might be reading their IgG or PCR lab tests incorrectly. Otherwise, they may never have suffered elevated CMV. Too many mainstream docs do not know how to read IgG tests. Still stuck in their medical school days, they mistakenly believe that only the short-term IgM proves CMV infection. In fact, elevated IgG levels can mean both long-term acute infection and presence of another acute infection, such as EBV or HHV6.
    Another vaccine that causes multiple diseases is Hep B vaccine. According to vaccine injury databases, Hep B causes Chronic Fatigue Syndrome, pancreatitis (without alcohol abuse) and colonitis, particularly in women and children. Any number of factors in Hep B vaccine, extracted from human tissue since 1986, could hamper brain function and memory.
    Also take into consideration damage to cells of the heart muscle, which cannot heal itself because it never stops beating until death.
    When I exert or attempt mild aerobic activity, my heart wall expands with blood that cannot exit the heart chamber to continue through vessels of my body. I develop tightness in my chest, shortness of breath, light-headedness, flashes in front of my eyes before I lose vision in one or both eyes, and I frequently faint. I successfully control most symptoms with specific Beta-blocker intended to treat Long QT Syndrome. Back in the early ’90s, before CDC classified, codified and defined CFS-ME, mainstream docs might have blamed my symptoms on autonomic nervous disorder, or that positive tilt test a year after Desert Storm cease-fire.
    Considering the plethora of health problems I suffer with general functionality short of aerobics or exertion, there is no doubt that more than one dysfunction of my brain and heart are to blame. Fortunately, I can look to military vaccines and battlefield exposures to find reasons I suffer such dysfunctions.

  5. Al-pal says:

    Dr Gary Kaplan, in his book “Total Recovery” (Rodale, 2014), pp 92-97, discusses the role that upregulated microglia play in chronic pain and depression syndromes. “Microglia act as the resident immune system of the central nervous system. If anything manages to slip past the blood-brain barrier, the microglia intervene. “Squeezing between tangles of dendrites and axons as they rush to kill the invader, microglia attack and devour any harmful organism. (quoted from R. Douglas Fields, “The Other Brain”, (New York, Simon and Schuster, 2010).

    “In order to protect the brain, the microglia secrete inflammatory chemicals to create swelling that acts as a buffer, as they work to destroy the invaders. While this inflammatory counterattack is going on at the molecular level, the person enduring it begins to feel sick with fatigue, headaches, fevers and achiness all over.” (Total Recovery, pp 95-56).

    Dr Kaplan researched microglia and found dozens of articles in medical journals, “each one linking microglia to a different stressor: physical injury, psychological trauma, loss of oxygen to the brain, bacterial infections, viral infections, environmental toxins. ” Thus, “When microglia are upregulated, they create widespread inflammation in the central nervous system. If they are turned on too often, they become hyperreactive,[sic], keeping the brain in a chronic state of inflammation.” (Total Recovery, p 96)

    Dr. Kaplan says PTSD,, anxiety disorders, and depression are all neuroinflammatory diseases in the brain. “What we’re just beginning to understand is that inflammation quickly gets complicated. Depending on how many cumulative traumas the body has endured, inflammation can spread like a brush fire. When it flares up in one pathway, it can ignite a secondary inflammatory response in peripheral pathways.

    Citing a study performed on teenagers who binge drank, that showed their microglia remained activated up to 10 years after they stopped drinking, Dr Kaplan says that this “demonstrates two very important concepts. The first is that the traumas we suffer have a cumulative effect. Every injury, every infection, every toxin, every physical trauma, every emotional blow generates the same reaction. Inside the brain, it triggers the microglia again and again and again.”

    “The second realization is even more startling. There comes a point when the microglia have been activated in such a way that they remain upregulated, continuing to spew out inflammatory chemicals even though the trauma that originally caused them to become active is no longer present. That response can show up in any number of ways: chronic pain, depression, anxiety disorders, fibromyalgia, chronic headaches, and PTSD, to name a few. ” (Total Recovery, pp 96-97).

    So the overactive microglia would seem to be the link between the muscle and the brain. I hope a lot more research will be done on this. And thanks to Dr. Kaplan for putting it together.

    Alison Wiltbank RN, FM/CFS patient

  6. nilaWilliams says:

    There has to be a reason that Blood Flow to the Frontal lobes are down when I have a flare up of CFIDS..I belive that my case is a post viral type of Immune dysfunction.. Ratio between T Lymphocetes and B surppressor Lymphocetes are out of balance on every test I’ve every taken. That my aneimia comes and goes plays into this also..Gaint Red blood cells and smaller vein openings could be part of the puzzle.. I do know that I have true inflammation of the connective tissues and any arobice exercise or exposure to the sun will bring on the flare up..We have so many studies on this disease and have spent endless money on silly things.. oh, for the doctor who gets the grant it is neccessary..
    Of course there is a muscle brain connection to the brain!! Just like there is a Brain that is the computer to our whole body!!
    All we can do is trust what others have tried and found useful..
    I will post more at a later time.. Explanations and my own formula to getting better with this misnamed illness.. God speed Nila

  7. reidjess says:

    You are still researching ways to treat symptoms. Twenty-five years after I was disparagingly diagnosed as ME/CFS, the cause is still unknown. The treatment of symptoms I have found most effective and cost-efficient is disputed by all but my soon-to-be-retired family physician. He took on my fight when none would on the behalf of his sister, going through what I was. When he sent me for a brain CAT-scan to make sure, more than anything, that he couldn’t be held liable for missing something, the overseeing neurologist called me into the screening room. That is NOT that hospital’s protocol. He further breached it by berated me for wasting public funds and told me to spend my own money to consult a psychiatrist to figure out my real problem. I told him HE should use his own funds to consult a proctologist to figure out his.

  8. not2care says:

    I was very active considering my illness…I didn’t realize I was so sick, because not one doctor would recognize my symptoms as anything but psychological…I rode horses most of my life, even competed most weekends, and pony clubbed in the summers…my collapse was total, completely bed bound for 1 1/2 years at age 52….so lack of exercise was not the reason I acquired ME/CFIDs..I also have fibromyalgia…before my collapse I had one episode that I can only explain, from my research, as cataplexy…by the time my doctor and the hospital doctors thought about how that might be the reason for my collapse, it was to late to diagnose..research says the test that is run needs to be done within 20 minutes..it was hours before a doctor ran his instrument across my foot to check my reflexes..but of course my doctor denies that it could have be cataplexy, because the test proved otherwise..makes one wonder what other idiot mistakes they make, how ignorant we, their patients must be, in their mind…actually I believe I just might have Chronic Lyme Disease..I lived in Virginia growing up and had several episodes of severe illness that I never had checked by a doctor because my father didn’t believe in them, he thought taking a child to the doctor “too much” would make him look like a bad parent…If I do, then I’ve had it for more than 40 years..good luck to me trying to get any kind of diagnoses now..I live in California and my doctor would not even listen to my history of illness from my time living in Virginia..my doctor won’t even diagnose my with ME, says because my tonsils aren’t infected..I DON’T EVEN HAVE TONSILS ANYMORE, they were removed when I was 7…I have pretty much every symptom that I’ve seen on every checklist for ME and then some..but MD doctor can’t seem to understand that I’m sick, disabled, and not much good for anything anymore..

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