Most experts agree that avoiding physical activity can compound CFS symptoms, yet exercise is also the very thing that can make symptoms worse! This catch-22 situation even has a name: “post-exertion malaise” (PEM), or post-exertion relapse, and it is considered one of the most debilitating aspects of CFS. It occurs not just with physical activity; mental exertion and any kind of stress can provoke a relapse of the classic flu-like symptoms of CFS, negatively impacting thinking and memory, and sleep for days or even weeks.
Yet no single research group has ever evaluated the effects of mental and/or physical stress on PEM in a multi-systemic manner, notes Dane B. Cook, Ph.D., an assistant professor of kinesiology at the University of Wisconsin in Madison. Now, thanks to a grant from the CFIDS Association, he and his team plan to do just that.
“The overarching theme is to understand the pathophysiology (or underlying processes) of PEM in CFS,” he says, including connections between the immune system, the brain, and behavioral outcomes such as fatigue. “This is a first step towards a more comprehensive understanding of PEM.”
Research Confusion on PEM
Current research on PEM is inconsistent and confusing, says Dr. Cook. It’s not even clear how much activity leads to PEM, or how long after the stressor PEM occurs. For instance, his group has performed maximum exercise tests in people with CFS and didn’t see any changes in symptoms until five days later, which may or may not have been related to the stressor. However, others have worked with participants in whom moderate exercise for 30 minutes increased symptoms 30 minutes to two days afterwards. Studies also use varying definitions and intensities of exercise, leading to significant variability in our understanding of PEM, he said.
Dr. Cook takes a psychobiological approach to the study of PEM, looking for objective markers that could trigger symptoms, He then uses exercise as a model to identify the effects of physical activity and other stressors on people with CFS. “That’s important, he notes, because you can’t begin to fix a problem like PEM until you can understand its underlying cause.
Comprehensive, Interdisciplinary Approach
Dr. Cook’s grant is unique in that it is designed to bring disparate research into a comprehensive whole.
The first piece of the puzzle comes from his own work using a special MRI that tracks oxygen uptake throughout the brain to identify brain function changes in CFS patients after they complete a fatiguing cognitive task such as repeatedly subtracting 7 from a starting number. He’s found significant differences in brain function of those with CFS and those without after such stressors, although there are no differences in brain function between the two groups without inducing mental fatigue.
The second piece of the puzzle comes from previous CFIDS Association grantee Kathleen Light, Ph.D., her husband Alan Light, Ph.D., and their team at the University of Utah. They identified unique post-exercise gene expression markers that can be used to differentiate people with CFS from those without and from those with multiple sclerosis and fibromyalgia. They also discovered increased expression of sensory and immune system genes after exercise.
The third piece of the puzzle is provided by another past CFIDS Association grantee, Gordon Broderick, Ph.D., of the University of Alberta in Canada. He used his previous grant to advance his work in identifying evidence of persistent immune activation after Epstein-Barr virus infection, which is thought to trigger CFS.
Dr. Cook monitors a volunteer as she performs the exercise challenge.
Together, the three groups will hopefully be able to begin to piece together the puzzle and create a clear picture of PEM, says Dr. Cook. “This grant is the outcome of many years of talking to other scientists about CFS and merging that information with other important findings,” he said. “It is really and truly an interdisciplinary project.”
The study has three principle components:
- Collect blood before and after a moderate exercise challenge on a stationary bicycle to evaluate and validate the expression of genes identified in the Light’s research.
- Use brain-imaging techniques to evaluate the structure and function of the brain during fatiguing and non-fatiguing cognitive tasks, focusing on areas of the brain associated with fatigue.
- Integrate gene expression and symptom data with the brain imaging results.
An important component of the study is the use of sophisticated mathematical modeling to integrate the disparate information that comes in from the different biologic systems (nervous system, blood, genes) to identify patterns and connections. The result, says Dr. Cook, is that “we can see systems ‘communicate’ (in the statistical sense) with one another and how that ‘communication’ changes when you introduce a stressor such as exercise.” If successful, he notes, the study will provide preliminary data to guide future large-scale studies targeting specific subtypes of CFS, determining the impact of PEM and identify potential targets for treatment.
Just the Facts
This study involves 15 women with CFS who will be evaluated over three days.
- On the first day, they will provide baseline blood samples, complete questionnaires about their symptoms and undergo a baseline MRI.
- On the second day, they will complete a 25-minute moderate exercise challenge, with blood samples, as well as symptom descriptions, taken prior to and 30 minutes post exercise.
- Twenty-four hours after the second day, participants will provide blood samples, undergo MRI, and again complete questionnaires about their symptoms.
Dr. Cook’s project is funded under the CFIDS Association’s Research Institute Without Walls (RIWW). We are grateful for the support of donors to the Catalyst Fund that fuel research projects like this one and others linked under the RIWW. Your donation of any amount will help sustain important research aimed at identifying better diagnostics and treatments for CFS. Our secure online donation center is available 24/7 at http://bit.ly/RIWW-fund. Thank you for your interest and support!
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Anyone who calls this disease CFS is destined to not understand it. We do not have fatigue. We are very sick with an untreated disease called M.E. Patients who have made some improvement have little or no fatigue. Fatigue is totally misleading and any study examining that is destined for the waste bin.
I hope you take into account the other studies showing that oxygen gets cut off to the brain for M.E. patients and 25 minutes of exercise is risking permanent brain damage.
I’m not sure what a mri would show, a pet scan is what I understand they use for the type of work. That said another good stress test would be to study the difference between how a healthy individual and a CFS patient react to alcohol and/or marijuana. The reasoning should be obvious to any suffer, we are sensitized to mold, gluten, and many believe chemicals. It sets something off in our nervous/immune system. From personal experience I cannot function from just a few hits off a joint. (I tried it to see if it would relieve symptoms which it did not) Even with a list in my hand I cannot perform simple task’s because I keep forgetting where I am walking to and what I am doing and I set the list down and lose it. Before I got sick I could easily function cognitively while stoned. It’s like it seriously inhibits the part of the brain responsible for these task’s.
Big controversy over this Greg…I do have CFS and I do get fatigued. If I exercise minimally I get a foggy brain, leg cramps, pain, and take to the bed to rest to recover. I spent 4 days in bed for a 10 hour day doing crafts and being on my feet. CFS is IMHO more accurate then the ME designation cause I don’t have a disease or -itis as that implies. Myalgic Encephalomyelitis is misleading in that -itis means something, germ, bug, whatever can be found and treated. Chronic Fatigue Syndrome is a composite of symptoms that define what is going on in my body. I don’t like CFS cause the medical field has caused so much negativity about the term because they think we are faking wanting drugs, sympathy, and/or we are lazy and stupid. I was an RN (retired) in a big healthcare facility and staff used to drive me nuts with their attitudes about Fibromyalgia, CFS/ME cause the patients didn’t look sick but were obviously hurting.
Have you read the article and listened to the video by Dr. Marvin Medow that Research 1st had on the blog a few days ago? It is called Brain Fog in CFS: What’s Going On? http://www.research1st.com/2012/06/11/medow-riww/
I wish there were groups around here researching these disorders cause I would so volunteer and give them my professional as well as patient centered input. It is a horrible disorder and I doubt if a cure will ever be found cause its symptoms and problems are so different for everyone.
Symptoms of PEM often occur several days after the exertion therefore to limit the study to three days means that most of the PEM will happen _after the study is over_ and not be measured or taken into account at all. This can lead to very skewed results and meaningless interpretation. Amazing that anyone studying CFS would not realize this.
Hi Bev,
Thanks for your comments about the study. Dr. Cook is actually trying to validate blood markers that did appear 24 hours after the exercise challenge in another group of CFS patients studied by Dr. Kathleen Light and colleagues at the University of Utah. You can read more about her study (funded by the CFIDS Association) at http://bit.ly/ROI-Light. The research group at University of Pacific has also shown measurable changes in CFS patients 24 hours after exertion. While PEM symptoms may not consisitently come on until more than 24 hours after the exertion, the effects of exercise on certain blood markers were measurable in the blood within this timeframe. In designing these studies, one also has to consider the imposition on the subjects, costs involved with extending a three-day study by several more days and the logistics of how to keep the experimental conditions as uniform as possible over that time. The intention is to identify a blood marker (or set of markers) to aid diagnosis and decisions about treatment in the clinical setting.
I agree with Greg. CFS is a serious illness. It needs a better name. PEM is real. If I overwork myself, several days later I need to rest for 4-10 days. Diagnosed at Mayo Clinic last year.
The Mayo diagnosed you with CFS/ME?! I was under the impression that.they take two days of your time and a huge amount of money, but leave you with no answers and no help.
It is unfortunate that the study is only lasting 3 days. My PEM symptoms can easily last longer than 3 days. Not to mention that the study is only including a small group of women. It seems reasonable that the study should be 5 – 7 days in length, include at least 10 – 20% men.
I strongly recommend that everyone inform ALL of their doctors about this website. Too many doctors have minimal knowledge of CFS, CFIDS, ME research — and instead just throw darts and a dart board when it comes to treatment approaches. My last primary care physician seemed to have ONE approach to wellness and that was graduated exercise. One approach. As much as I would explain the severity of symptoms it brought about, he continued to push this method of treatment without listening. Then, because I wasn’t immediately responding to a CPAP (sleep apnea machine) trial, he said that my poor sleep was depression related. This was in direct contradiction to the sleep specialists he had sent me to which said that CPAP machines can take a year to respond to.
Many doctors are truly clueless when it comes to how to treat CFS and want to just label symptoms as depression related or similar. Yes, severe depression can be caused by CFS. But, many doctors are still YEARS behind when it comes to being aware of the facts… and what it is truly like for a patient to experience this debilitating disease.
Remember that our doctors work for US and we need to encourage them to research CFS.
I agree, its so sad, when they look at you like you are crazy. I went to a cardio doctor to see if i could get tilt table test to see irregularities, he refused to do it and wanted to do exercise stress test. I refused to do that cause i didn’t want to relapse and end up in bed for 3 days. I brought in paperwork i printed which he wouldn’t even look at and mocked.
Then to top it off, I get a bill in the mail from him.
Yes, Mayo will diagnose ME/CFS but the clinic is in the dept of Psychiatry.
I have the SOB, diaphoresis, and sudden onset pain in my back with 3 minutes on the treadmill, second day. Once the symptoms are felt, I have seconds to sit down or I will faint. I will have a 3-4 day flair up afterwards. No one is mentioning what happens to you as your exercising, running a sweeper, or walking from your car to the building. Are you able to tolerate the activity as you are doing it?
A very valuable contribution, thank you!
You must find a way to measure stress, that is the only way. Sometimes for me just one perplexing question by a client can bring on PEM for me. Of course I always have PEM after giving a presentation (which lasts 1 hour), luckly i have still been able to do them for the past year. The body aches and headaches and pain has increased so much this past week, and my skin hurts too, which is horrible. God and heaven help us…please change the name of this illness, its not humane.
I have been dealing with all of CFS,diagnosed myself! I also have an immune disorder that I give myself infusions once a week. I also have many different types of arthritis and fibromyalgia. And….. On and on! Anyway who Ora where would you go to get this diagnosed!! I’m at my wits end with this!