PEM isn't a Mystery

PEM isn't a Mystery

PEM may be the hallmark of ME/CFS, but it is not fundamentally underpinned by a pathology shrouded in medical mystery, evading thousands of studies and an even larger number of patient workups. It only seems that way because the phenomenon has been medicalized, legitimized, and reinforced by thousands of patients’ collective experiences of their subjective symptoms. PEM is the boogie man of ME/CFS. A boogie man, that, if triggered, could result in the permanent worsening of a patient’s life. (pretty high stakes, right?)

At its core, PEM is an increase in symptoms following doing too much. Too much can be sensory, emotional, mental, physical, social, or environmental. But this increase in symptoms is just that, an increase in symptoms. It’s the body’s reaction to the brain saying "too much!" A stress state. It is not dangerous in and of itself. There is nothing doctors have found in patients’ bodies demonstrating damage from PEM, or any other disease process in ME/CFS. A patient could crash to the point of not being able to move for years, and yet blood tests would still be nearly, if not, indistinguishable from that of a perfectly healthy individual.

The symptoms that define the subjective experience of this stress state (PEM) are enigmatic, like everything else in ME/CFS. The onset, triggers, duration, and actual symptomology of PEM vary immensely between people. Some people get PEM from listening to music, having the wrong person in the room, a new medication, eating the wrong food, watching a movie with a plot that is too complex, going outside, boredom, excitement, crying, laughing, cold, humidity, environmental changes, or even being too animated in a conversation. (These are all real examples.)

Some experience PEM immediately, while for others it arrives days after the offending activity. It can last for hours, days, or even weeks. There is no consistent pattern beyond “something is interpreted as too much and the result is that some set of symptoms occurred thereafter, for some length of time”. Many find themselves in PEM without cause. This is usually explained to the person that the presence of PEM indicates in and of itself, that they are doing too much and need to lower the amount they do.

PEM can be severe, to the point where one is unable to speak or move. How can we possibly link the vast array of PEM causes listed above to the generation of states that can be this severe, which last for days, weeks, or sometimes months? How can having a too-lengthy phone call, 3 weeks ago, reduce muscle strength to zero and render one unable to speak? What physiological process could possibly be mediating this?

It’s simply the mind in a fear state producing and perpetuating sometimes-severe symptoms, and that tension drives further vigilance and fear, which makes you feel horrible. The length of the phone call didn’t push a body to the point of breaking. It was the expectation and fear of too much, which drove the nervous system into FFF and the symptoms along with it. Then the FFF response is fueled by a mind dominated by fear and hypervigilance of these symptoms. A mind inundated with questions surrounding how bad it could get, if you’ll end up on a feeding tube, if you’ll ever recover or if this is your new baseline. Then add in the feelings of regret for having done too much when you should’ve known better and the fiery frustration at the limitations of ME/CFS, and you are in a dire state of distress.

What is too much to someone, and therefor causes PEM, is not too much to someone else. Too much is one’s mind’s unique interpretation, drawn from past experiences, current state, beliefs around the causes of PEM, one’s understanding of ME/CFS and PEM, along with expectations regarding what may happen following too much. So, when one steps over their unique line of too much, they experience their unique consequences, informed by all of the above.

The great news is that PEM is not a serious, mystery physiological response to a mystery disease process that has evaded all detection. It is a stress response. It’s mediated fundamentally by the brain. And the brain is plastic. And these behaviors and responses can be unlearned. There is absolutely no scientific basis or physiological process which can explain why listening to a song, watching an engaging show, or being in the same room as someone you don’t like, would cause weeks or even months of “neuroimmune” dysfunction and symptoms so severe that the ability to speak is lost. PEM is unique to the individual, benign, and unlearnable.

Ativan?

One of the more interesting things I’ve seen is that commonly patients are prescribed ativan to pre-emptively block PEM. Amazingly, patients report that it works! Now, if PEM is some physical machination of neuro-immune or mitochondrial dysfunction, why would a benzodiazepine be the most effective drug at blocking/preventing PEM? Well, it’s because PEM is FFF, the result of fear and hypervigilance around anything that may cause symptoms. And Ativan is incredibly effective at dampening the brain’s response to fear.

2-day CPET?

So what about the “smoking gun” of the 2 day CPET which proves that PEM is physiological? Well, there has never been a double-blinded, large scale study, wherein any of these conclusions have been replicated. Like most of the research in the ME/CFS field, it is one off, small sample sizes, small effect sizes, occasionally questionable methodology, and large promises which have not translated to anything approaching a diagnostic, underlying mechanism, or treatment in practice.

But some studies do show a small change between ME/CFS patients and controls during the 2 day CPET, so I’ll speak to that. You have patients who are deeply fearful of exercise and the consequences and PEM that may follow. You then have them complete an abnormally large day of exertion on the first day, which I’m almost certain their body will respond to due to the fear and expectations around catastrophic responses. When they go to do the second test, almost certainly their brain and therefor body will be pumping the brakes due to all the stress of the first day. (ie. the Central Governor (opens in a new tab) theory)

So how do people get PEM who didn’t even know it existed?

You don’t actually have to know about the existence of PEM, which is a construct made up to describe a loose pattern of symptom emergence, to experience symptoms generated by the mind or be bogged down by a body that is constantly in FFF. These are things that everyone will experience at some point in their lives.

For example, if you live in a highly stressed, pressurized state for long enough, eventually your mind/body does shout too much!. And symptoms like PEM is the response to tell you to slow down. But it’s not actually “PEM”, it is simply a stress response, of a mind and therefor body that are at their limit. Alternatively, PEM can be generated and perpetuated, SOLELY by preoccupation and fear of symptoms.