Thread by @PutrinoLab

Wanted to put forward a thread about #PEM since there have been some new developments and also because I just need to get some of this out of my head and work through it. Folks with infection- and exposure-associated chronic illnesses (IACIs) like #LongCOVID, #MECFS, 1/

chronic #lyme and other tick- and vector-borne illnesses will often experience post-exertional malaise (PEM). In fact, it is often thought of as a cardinal hallmark of many of these diagnoses. To start, a simple working definition of PEM: it is a condition that emerges when 2/

somebody physically, mentally or emotionally exerts themselves beyond a certain point, causing a delayed worsening of symptoms that can last days, weeks or even months. NB: There is much more to PEM than this definition, and one of my favorite explainers is @LongCOVIDPhysio's 3/

work: :

PEM also has some other names that are used interchangeably. We're going to stick with PEM as it is the most commonly used, but people also use Post- Exertional Symptom Exacerbation (PESE) and Post-Exertional Neuroimmune Exhaustion (PENE) to 4/

discuss PEM. So let's dig into some physiology and history. PEM is a controversial topic: not because people with IACIs haven't been explaining PEM consistently and patiently to clinicians and researchers for decades, but because many clinicians and researchers have not had 5/

the scientific tools, the intellectual curiosity or (I'll say it) the general decency to look beyond our internalized biases and work the problem beyond prescribing anti-depressants and graded exercise. Decades of this, all the while with patients suffering, worsening under 6/

our care and being medically traumatized and gaslit to boot. A truly shameful history that continues to this day. Characterizations of PEM as "functional" (previously known as 'hysteria' before the rebrand) or psychological (unhelpful illness beliefs) have done more damage to 7/

more people with IACIs over the years than I care to imagine. So lets shed some light. Firstly, lets transparently name the fact that PEM is not a well-characterized condition. Again this is not due to patients not being consistent about what is happening or good-faith 8/

researchers not working admirably on the topic over the years, it is just largely misunderstood or conflated with other symptoms. For instance, PEM is NOT THE SAME as fatigue, exercise intolerance, or excessive sleepiness but when PEM is triggered, it can certainly cause these 9/

things. If you're a clinician reading this, and you have a patient in front of you describing symptoms that sound like PEM, you need to disambiguate PEM from other symptoms - **not all fatigue is PEM**. Use gold-standard patient reported instruments such as the DePaul Symptom 10/

Questionnaire PEM short form (DSQ-PEM) to screen for PEM, the FUNCAP27 to measure the impact of PEM on daily life, the Fatigue Severity Scale to measure the impact and presence of fatigue and the Epworth Sleepiness Scale to measure for presence and severity of sleepiness. We 11/

also have objective measures that should not be undertaken lightly, since I want to transparently name that some patients have reported worsened symptoms after undertaking them and also they are unsuitable for severe or very severe folks, but 2-day CPET and invasive CPET have 12/

both been used to objectively measure the presence and severity of PEM and potential mechanisms related to PEM, respectively. Since we brought up CPET, let's talk about the relationship between exercise and PEM. People try to make this complicated, but it isn't. Let's dive in 13/

In this thread, 'exercise' will be defined as: physical activity that is being performed with the intention of improving cardiovascular fitness or muscle strength. 'rehabilitation' will be defined as physical activity that is being performed with the intention of safely 14/

restoring function and reducing impairment. When PEM is present: prescription of exercise is inappropriate, prescription of rehabilitation *may* be appropriate. This is the point where a lot of folks who treat patients with postural orthostatic tachycardia syndrome (POTS) 15/

will tell me that exercise helps their patients with PEM, and this is the point where I reiterate: not without rehabilitation first. POTS and other dysautonomias can frequently drive PEM, and according to the AAPMR and others, as many as 70% of people with IACIs may meet 16/

diagnostic criteria for POTS, so it is something we must screen for in every IACI patient. Here's what is accurate. If you:
- have POTS that causes PEM
- have PEM that is *solely driven* by autonomic nervous system dysfunction
- are rehabilitated carefully
you may be able to 17/

progress to exercise after successful rehabilitation. Unfortunately, many folks with IACIs have PEM that is driven not just by POTS alone, but by other biological factors. This means that rehab alone is not suitable for them and this also means that trying to push them into 18/

exercise before they are ready will invariably cause harm. In 2021 we started publishing and distributing educational guidelines about this because folks were identifying a lot of POTS in #LongCOVID patients and they were using existing POTS rehabilitation protocols: Levine 19/

protocol, Modified CHOP, Buffalo Protocol. All fine protocols that have helped POTS patients in the past (that our team has used frequently, btw!) who don't have some of the additional immunological, environmental and microbial drivers to their PEM that folks with IACIs do. 20/

Before we move on from POTS and PEM into some of the other drivers, the main difference we made to the traditional POTS rehabilitation paradigms was shifting to what we called "symptom-titrated physical activity" - so rather than following a traditional protocol that says: 21/

"maintain workload at x% of max heart rate for y minutes for z days/weeks and then progress to a/b/c", we personalize the intensity of the POTS rehabilitation protocol to symptoms occurring during rehabilitation and that may be triggered after the session. This simple shift 22/

has allowed us to safely rehabilitate many folks who would have failed to complete more traditional, rigid clinical protocols that are not symptom-titrated. But what about other drivers of PEM? What if you don't have POTS but still have PEM? What is going on there? Our most 23/

likely next culprit is your energy production infrastructure. I don't tend to just think of this as your mitochondria, but also think of this as the way your body distributes energy (blood vessels) and takes out the trash (lymphatic/glymphatic system), and this is where 24/

research into the physiology of PEM is starting to get really interesting. As I write this, I realize I'm now at 25 tweets which appears to be the limit. I'll leave you hanging for a moment, but hope this has explained some of the thinking around PEM and physical activity.🙏/end