Guest Post: Dr Larry Baldwin on Post-Exertional Debility in ME/CFS

Dr. Larry Baldwin is a licensed physician (B.A. Johns Hopkins Univ., M.D. U of MN- Minneapolis, general surgery residency Marshfield Clinic- St. Joseph’s Hospital, Marshfield, WI) who practiced general and vascular surgery in Hibbing, MN until myalgic encephalomyelitis (ME) suddenly ended his career with a severe, acute viral illness onset twenty years ago.

In April, Dr. Baldwin worked with our Scientific Director, Suzanne D. Vernon, PhD to provide comment on post-exertional debility to the Institute of Medicine Committee on Diagnostic Criteria for ME/CFS. The Association has been working with Dr. Larry Baldwin, tapping into his medical expertise and experience as a patient.

We are happy to provide his insights here as a guest blog post, as he talks about post-exertional malaise (PEM) as Post-Exertional Debility (PED).

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Post-Exertional Debility is an Important Symptom during Myalgic Encephalomyelitis
By Larry Baldwin, M.D.

I have pursued a variety of research interests such as: synthesis of an organic molecule designed to release nitrogen gas as a preservative, health care delivery issues at the Johns Hopkins Hospital Pediatrics ER and at the rural medical clinic in Onamia, MN, health care policy concerning the competitive environment for the teaching hospitals in the Twin Cities Metro area, and the early use of thrombolytics in acute lower limb venous occlusion to prevent chronic venous disease. So I was interested in using my research observation skills to study my own ME/CFS symptoms and have kept a record through the years.

From this record I see a pattern of symptoms, which I call post-exertional debility (PED), that occur following physical or cognitive exertion. This pattern is specific and vastly different from any post-exertional experience I had as an athlete, surgery resident or while practicing surgery. While training for marathons I was able to run through the “wall” that many runners experience. Now I experience a similar wall after minimal exertion and have not been able to train through or push through this wall.

This pattern of post-exertional symptoms has been very consistent while experiencing them almost daily during 20 years of disease. The onset and peak severity of symptoms is characteristically delayed following exertion. The symptom severity increases as the workload intensity and duration increases. Some symptoms appear only as the workload increases. This symptom pattern is different from that during an acute viral infection.

The following table shows how symptom severity increases and symptoms appear as workload increases. Workload may be physical or cognitive. The lowest level of workload will elicit migraine pain, fatigue sensation, cognate impairment and sleep onset prolongation. As the workload increases these symptoms increase in severity. At the next higher level of workload sleep abnormalities worsen with nocturnal myoclonus beginning and then worsening as workload increases. This has been severe enough, on occasion, to cause me to fall out of bed. Mild workload will not cause noticeable neutrally mediated hypotension, but at higher levels it occurs typically after a few hours of sleep at night. As the workload increases the hypotension is more severe, lasts longer and spreads into the daytime hours with greater interventions needed to treat it.

PED Symptom Chart

Earlier in the course of the disease, salt tablets, midodrine, mestinon, florinef and approximately 4 liters of water per day were needed either singularly or in various combinations to treat hypotension problems.  With weight lifting for muscle development and presumably some degree of atherosclerosis now only water is needed to maintain blood pressure. Thermoregulation and nasal congestion seem clearly linked to exertion with some change in severity with change in workload intensity but the gradations are more difficult to notice. Asthma is correlated to workload changes but it takes a certain amount of work before it appears. Even more workload is needed before gait impairment occurs but when it appears it is either a distinct limp with a positive right Trendelenburg sign due to muscle weakness (when standing on only the right foot, the pelvis tilts downward on the left side) or severe enough where I am unable to walk until I rest recumbent for about an hour after which gait is much improved.

Neuroimmune exhaustion is a very severe form of PED occurring only after prolonged physical exertion at high workload intensity, such as driving a machine 4 hours a day for three days consecutively. This can occur after prolonged cognitive exertion as well, typically 5 to 7 days of concentrated cognitive work for two to four hours a day recently although I could work longer before this happened earlier in the disease. If rest does not occur when exhausted, then viral infection certainly occurs and this can lead to bacterial infection such as pneumonia if I continue exertion. This occurred a couple times before I learned this sequence. I was impressed that exertion can cause such significant immunosuppression.

As mentioned, the onset of PED begins gradually but the peak symptom severity is typically six to eight hours after the majority of the day’s exertion has occurred. If the exertion is prolonged for a few days such as occurs on a camping trip, then the peak symptom severity occurs two to four days after the trip ends and last much longer, typically two to four weeks.

Post-Exertional Debility Symptom Pattern

The following radar chart takes each symptom and compares the typical maximum symptom severity that occurs during post-exertional debility versus during an acute viral illness.

Slide1

Approximately ten to twelve viral illnesses per year provide ample observations for comparison. The viral illness is usually severe enough to limit exertion which largely explains the difference in symptom pattern. Exertion is much more likely than a viral infection to cause severe: migraine pain, sleep abnormalities, orthostatic hypotension and gait impairment, which highlights the importance of distinguishing exertion-related symptoms. GI symptoms and neuroimmune exhaustion rarely occur during a viral infection.

It is also significant to note that most of the symptoms are consistently more severe following exertion, whether it be recreational or engaged in more arduous family business, than during an infection and the opposite would be seen if the disease were due to abnormal health beliefs.

I approach exercise as training during chronic disease with the goal of being as fit as possible to maximize what I am able to do and to attempt to increase cardiopulmonary endurance. My residency training was interrupted by lyme disease with cardiac and neurologic complications requiring long term IV and oral antibiotics for cure. Ten months of challenging physical rehab was needed which began with me standing for five minutes followed by two hours of sleep. Eventually I was able to complete the final two years of a demanding residency training and succeed at practicing surgery.

Fourteen years ago I was well enough to start exercising slowly. For the past five years I have been gaining muscle mass and some endurance. Compared to the previous rehab experience during residency, I am now putting in much more effort, the gains are smaller and much harder to achieve, either because of older age and/or a different disease mechanism. (The previous clinical, lab and radiologic evidence of lyme disease are long gone and now I have clinical, ganglion antibody and low epinephrine evidence of myalgic encephalomyelitis.)

Symptom Pattern Difference during Post-Exertional Debility versus Acute Viral Infection

Discussion
There clearly is debility following cognitive or physical exertion during myalgic encephalomyelitis that is a specific symptom or pattern of symptoms. I suspect there is variation between patients with idiosyncratic symptom patterns for individual patients. In contrast to a vague description such as malaise, post-exertional debility would be a more appropriate term for this symptom.

The delay of the onset of PED symptoms seems to be a useful clue to the pathophysiology. A process that takes several hours to begin and lasts for several hours has multiple causative candidates but if it involved micorglia and astrocytes seen on PET scans performed by the Japanese researchers these immune cells located around the thalamus, hypothalamus and pons may secrete cytokines and chemokines and begin a cascade of events involving oxidative and nitrosative stress spreading to the rest of the limbic system either directly or via interconnecting neuronal tracts. This scenario could be one way of explaining the PED timing and many symptoms since an inflammatory cascade can take time to occur, can persist and could create an environment of heightened excitation which in the thalamus can cause more pain, in the hypothalamus can overstimulate the pituitary leading to down regulation and lower hormone production, such as hypocortisolism during stress, and through connections to the autonomic nervous system could lead to low blood pressure issues and problems along the widely distributed vagus nerve.

An inflammatory environment around the hippocampus and its connections could explain difficulty forming short term memories, and slower information processing speed. Involvement of the amygdala could explain the hyper aroused state often felt after exertion described as being, “Tired but wired.” Pontine involvement could explain a variety of sleep abnormalities. These specific areas need not be directly involved with inflammation but their connecting tracts may be affected sufficiently to cause symptoms. If the exertion workload is increased to a point that a type of adrenal exhaustion occurs this could explain a larger delay and further symptom prolongation and still be consistent with this hypothesis.

Somehow the body senses that physical (muscular) or cognitive (nonmuscular) exertion has occurred and then triggers a symptom response. The brain makes it possible to perform the exertion and if part of it is itself inflamed then the brain is what initiates the process leading to symptoms. The observation of the high consistency of exertion followed by PED is consistent with this. It will be interesting if further studies support a limbic-pontine encephalitis hypothesis.

Other explanations for the delay of peak PED symptoms could be a multi-step process, an accumulation of molecules before a signal is triggered or the opposite, a depletion of molecules before a signal is triggered. The process may involve an mRNA transcription which takes a signal to begin and once begun requires a certain amount of time to complete. Feedback loops must exist that perpetuate the disease such as a possible cholinergic-immune reflex that connects the autonomic nervous system to adrenergic receptor on immune cells, oxidative and nitrosative stress. Genetic abnormalities may be a fairly ubiquitous interplay that is involved in the initial disease trigger and what keeps patients from slipping back into health.

Eventually the pathophysiology will need to include an explanation for the delay of the onset of PED symptoms and therefore post-exertional debility should be included in the definition of myalgic encephalomyelitis as a guide for research and clinical studies. Ambulatory monitoring with relatively inexpensive smartphone-connected devices may provide opportunities to collect “Big Data” of patient’s symptoms under various workloads compared with controls to further characterize the nature of post-exertional symptoms.

May 14, 2014
  • tomkindlon

    Interesting. However, “approximately ten to twelve viral illnesses per year” is quite a lot: I wonder are some of these in fact relapses of the ME/CFS in which case it isn’t easy to make a distinction between post-exertional debility and infections. I have come across people who were trying to exercise who were classifying symptoms as new infections when they seemed to me to be just as likely to be due to overdoing it.

  • Interesting indeed! I’m glad to see a push for doctors/patients self collecting data as this is such a useful tool.

    Most interesting is the mention of nocturnal myoclonus…I experience this at times as well but never attributed it to my CFS or hypotension. Makes sense! When it occurs, I too jump from bed.

  • John

    I like the following idea from the article- “In contrast to a vague description such as malaise, post-exertional debility would be a more appropriate term for this symptom”. Any chance to improve the terms used to describe/label the disease and its symptoms in order to make them more descriptive and accurate should not be missed.

  • Suzanne D Vernon

    Hi Tom, I will relay your comments to Dr. Baldwin and let you know what he says.

  • Suzanne D Vernon

    Hi Tom, I am posting Dr. Baldwin’s response to your comment. Hope this
    helps clarify. (For me) it underscores the importance of understanding
    how each individual experiences ME/CFS, sharing that experience and
    learning from it. Thanks for the insightful and constructive comment!

    From Dr. Baldwin:
    Viral
    infection symptoms during ME are distinguished from PED symptoms by
    multiple factors such as: the infectious symptoms usually occur during
    the flu season, someone else in the family has the infection before I
    get the symptoms, there are accompanying viral symptoms such as chills,
    sore throat and/or rhinorrhea, the viral symptoms do not occur after
    exertion so they are not PED symptoms, the viral symptoms last many days
    or a week which is consistent with a viral infection.

    I have
    experienced one episode of post-exertional viral-like symptoms which
    occurred during the summer, when no one around me seemed to have a viral
    infection, but the chills, rhinorrhea and fatigue lasted only 8-12
    hours post exertion followed by resolution. So I think this phenomenon
    may exist, but I feel there is a clear distinction for me between PED
    symptoms and post viral infection symptoms.

    • tomkindlon

      Thanks to Dr. Baldwin for taking the time to reply.

  • Tanya Selth

    thanks Larry, good article. I hope people who dont have this illness pay attention to your article as it makes it clear that fatigue is just a small part of our illness and that they should putting most of the focus on just fatigue when its just a small part of this illness. Like you, Ive been getting asthma from it.. its like I get a viral reaction (unknown virus) when I start to crash and then this can set off asthma. I get more stuffy noses when Im in a flare up too.
    I also had double pnemonia too and ended up in hospital. I get more suspectable to other things eg viruses, bacterial, fungal issues the worst my ME is (m currently dealing with a big patch of thrush on my torso).
    Im currently Im needing to be ambulanced to hospital once a month and ending up there, due to ME and its complications. My doctor is about to write out a plan for the hospital because once I end up there, they dont always know that I need to be given a drip. My kidneys are at risk now according to blood tests as I get dehydration with this illness.
    This illness is crazy (I get over 90 symptoms with it) and for those who refer to it as just a fatiguing illness, that is completely insulting when some of us are getting so very sick with it and with some of us like mself, it is actually putting our lives at risk. Last time an ambulance had to be called less then a month ago, I was so weak that I was having to be held up in bed just to drink and couldnt get to the loo. Id spent all night trying not to wet the bed.
    Im glad too that you pointed out that your autonomic issue wasnt stable but came in with the illness and worsened with it. I suspect my POTS worsens with my ME flares thou its hard to say.

  • Tanya Selth

    sighs.. my response.. it was supposed to say that they shouldnt put all the focus on fatigue.. and not should. augh!! the ME brain saying the opposite to what is meant.

  • Mark

    A very interesting blog given Dr Baldwin’s background and I was particularly interested to read how he considers that the recent (small study) findings of neuroinflammation might explain many of the symptoms of ME/CFS including the delayed exacerbation of symptoms. I’ve a strong feeling that this may be a key central mechanism that helps explain the heterogeneity of symptoms and of onset.

    I wonder if Dr Baldwin has considered if the initial ‘viral onset’ and subsequent apparent viral illnesses may instead be symptomatic of an already established state of glial activation?

  • Pingback: PEM/PED and… | Susan Thompson's Medical Blog()

  • Dianne Timbers

    I haven’t kept as careful records as Dr. Baldwin has but I have noticed, in me, a relatively consistent progression of symptoms depending on how badly and for how long I overdo. I try, not always successfully, to use the first indicator, trouble getting to sleep, to slow me down. Happily, some of the worst symptoms, such as hallucinations, seem to have disappeared completely or are only hints of what they used to be. I’m glad to see an increasing emphasis on the post-exertional problems. They have always been the heart of my illness, the hardest for me to deal with, and the hardest to explain to others.

  • burcosco

    Interesting to know whether active sarcoid or post sarcoid fatigue patients were used and whether a shorter lived PEM might have been observed among the sarcoids if exercise taken at say 6 and 12 hrsintervals.
    Also whether PEM of delayed type only appears after resolution of e.g. Lyme.
    Is delayed PEM unique to CFS, common in CFS or universal in CFS (and if the latter whatof patients whoa re braodly CC/ICC consistent for ME/CFS but differ on this single parameter?) Including it as one criterion is great, excluding folk who don’t meet that one criterion is imo dangerous.

  • MR AIDAN G WALSH

    ‘internal ionisation radiation injuries’ broken chromosone & translocations this illness is radiation sickness absolutely nothing to do with bogus Lyme