Open DSQ PEM survey - DePaul University, open October 2025

[TheDePaulGroup]

Hello all,

I am part of the team that created and deployed this survey (DSQ-PEM 2). I have been reviewing all the feedback across forums, comments online, and comments left on the survey. I would like to pass on a message from Dr. Leonard Jason:

I would like to thank the patient community for their participation in our recent surveys—one focused on criteria for measuring illness severity and burden, and the other on post-exertional malaise (PEM). More than 4,000 individuals responded to the first survey, and over 600 to the second. My team and I are deeply appreciative of this remarkable response and the thoughtful comments we received. Several participants asked how we have collaborated with patient groups on these and other efforts. Below, I provide a brief overview of this broader participatory process, followed by the rationale for doing our two most recent studies.

For more than 35 years, our group has been privileged to work closely with the patient community on a wide range of initiatives. Beginning in 1990, patients alerted us to the harm caused by the CDC’s inaccurate prevalence estimates and the stigmatizing media portrayal of ME/CFS as “Yuppie Flu.” With financial support and encouragement from the largest patient organization at that time—the CFIDS Association—we conducted a pilot study that challenged the CDC’s estimate of only 20,000 affected individuals. With these pilot data, we were able to successfully obtain NIH funding, and we carried out our community-based epidemiologic research demonstrating that ME/CFS prevalence was far higher than originally reported. The effort took our group a decade. This major shift in understanding the prevalence of ME/CFS would not have been possible without the sustained engagement and guidance of the patient community. When patients raised concerns about the stigmatizing effects of the term “chronic fatigue syndrome,” we conducted research showing that labeling indeed influenced public perceptions—validating patient experiences and supporting the use of “ME” as the preferred term. These two foundational projects were both patient-driven. More details on this early collaborative work can be found in: Jason, L.A. (2015). Ethical and diversity challenges in ecologically sensitive systems-oriented interventions. American Psychologist, 70, 762–775. PMCID: PMC4863698.

In part due to these efforts, I was later appointed Chairperson of the U.S. Research Committee of the CFS Advisory Committee, which advised the Secretary of Health and Human Services. At those meetings, patients repeatedly voiced concerns about the limitations of the Fukuda criteria used in research and clinical trials. Guided by these concerns, our team spent the next decade evaluating the adequacy of these criteria. We found that many studies using Fukuda’s definition recruited participants who did not experience PEM or cognitive impairment—core symptoms of ME/CFS. Moreover, the criteria relied on symptom “occurrence” rather than precise frequency and severity measures. Our research demonstrated that such measures failed to distinguish ME/CFS from major depressive disorder, while frequency/severity metrics could make that distinction.

Addressing our work on measuring post-exertional malaise (PEM): The original DSQ was not designed as a comprehensive PEM measure, though it included ten relevant PEM items. Rather, it was a measure of the multiple symptoms that occur among patients. Just before the pandemic, we published what we call the DSQ-PEM, a short PEM tool derived from the DSQ survey. But this brief scale did not cover key issues such as the delay of onset of symptoms and triggers for symptoms. Recognizing the need for a more complete instrument, we sought patient input through social media, inviting suggestions for additional questions and refining the measure iteratively based on feedback. Once a patient-led effort had developed the PEM questionnaire, we then posted it on my Facebook account, and 1,534 patients completed the resulting comprehensive PEM questionnaire. Details on this patient-generated measure are available in:
Holtzman, C.S., Bhatia, S., Cotler, J., & Jason, L.A. (2019). Assessment of post-exertional malaise (PEM) in patients with Myalgic Encephalomyelitis (ME) and Chronic Fatigue Syndrome (CFS): A patient-driven survey. Diagnostics, 9(1), 26. However, it is a lengthy questionnaire of 8 pages.

When the pandemic began, few validated PEM measures were available, but as we know, PEM is a key symptom of Long COVID. As there were very few PEM-validated measures at the time, Long COVID researchers worldwide adopted our brief 5-item PEM scale and the 10-item DSQ-PEM, both of which have since been translated into 28 languages. These instruments that been used in dozens of articles over the last few years. However, our comprehensive 8-page PEM questionnaire proved too lengthy and was not used by researchers. This led our group to explore whether a balanced, intermediate solution could be developed—a more current and comprehensive measure than the DSQ-PEM, yet briefer and more practical than the full 8-page version. Using data that we had already collected on the 8-page version, we just examined core PEM domains, so we were able to keep it to 2 pages. We finished this study in the summer, and it has been accepted for publication in a journal. We are now working on the page proofs, but it will be released shortly.

After finalizing this briefer version, which we now call the DSQ-PEM2, we wanted to collect new data with this briefer PEM instrument. That is the instrument that I circulated last week on my Facebook page, and the items originally had been recommended by patients when we created the more comprehensive 8-page instrument, but of course, it was briefer at just two pages, with the hope that this briefer instrument might be used by investigators, and it certainly is more comprehensive than the DSQ-PEM that has been so widely used.

I also want to acknowledge the thoughtful feedback we have received regarding this new PEM instrument, and all comments are being carefully reviewed. Some participants mentioned they would have preferred to be able to skip items, and several respondents requested more details clarifying items. Several mentioned it was difficult to differentiate a PEM occurrence from the overall ME experience, and this certainly is a difficult task to differentiate in a self-report questionnaire. While we did include a question about whether pacing was effective in reducing PEM, we did not ask for each question what it would be like if a patient were not pacing, but to do so would have doubled the number of questions on our brief 2-page questionnaire. These suggestions reflect fundamental measurement issues and reinforce that operationalizing PEM in a way that matches lived experience remains a challenging process for these types of surveys. However, self-report questionnaires do have the advantage of being less expensive than many other methods, such as two-day cardiopulmonary exercise tests.

We are immensely grateful to the more than 600 participants who completed the survey. Although this version (the DSQ-PEM-2) is less detailed than the 8-page comprehensive measure, we hope it will serve as a practical and scientifically valuable tool for future research on PEM. Fortunately, there are more PEM instruments today than when we began working on the creation of DSQ in 2009.

Warm regards,

Lenny Jason

 

[Hoopoe]

I also wanted to add my special perspective as person who used to be much more sicker and can now do physical activities but who still considers himself disabled.

My feeling is that questionnaires are failing to capture the limitations that I still have because they ask questions such as "can you do x?" or "if you do x do you suffer PEM?" or "how limited in doing x are you". These questionaires go through a list of important activities and ask these questions for each activity.

I think these kinds of questions are not capturing the essence of what PEM is.

It does not matter that much what activity x is.

What appears to matter is how sensitive someone to PEM is, and the cumulative effect of activities that each contribute to triggering PEM. Each of these activities might be tolerated on its own.

We should be asking people whether they are FORCED to maintain an overall activity level (after explaining what is meant) that is lower than they would like, because of PEM (after describing the phenomenon). If they answer positively, we should ask them whether they can recognize this as something that happens again and again, and how long this has continued to happen.

By activity level I mean how much a person does over the course of the day. Have they shifted from more demanding activities and more hours per day dedicated to these and other activities to less demanding ones and more hours per day to rest or restful activities?

 

[Kitty]

I can't really see anything that looks useful or meaningful after the first four questions (and as @Trish says, the first question does need some clarification).

Before answering any further questions I'd like to know what it is they're actually trying to find out and why. Without knowing that it's really hard to assess the suitability of a questionnaire. At face value this one mainly appears to be asking whether people get PEM, which is a Yes/No answer. It's fair enough to add two or three supplementaries to probe whether what the respondent means by PEM is roughly the same as the investigator, but beyond that I start to get lost.

I'd also decline to give information about my racial background or education history on a form like this. Unless there's a clear explanation of why it's necessary, I'd assume it falls into the category of unnecessary and intrusive information that European data protection regulations strongly dissuade organisations from collecting.

 

[Utsikt]

@TheDePaulGroup

While I appreciate the response, there is nothing in the post that addresses some of the serious issues raised by e.g. Trish and other members in this thread.

There seems to be a profound confusion about what PEM is, and maybe more importantly what it is not. I personally do not at all feel confident that the PEM2 questionnaire is able to sufficiently weed out false positives.

Surely the purpose of such a questionnaire is to try to sus out of the person actually has experienced PEM, not just ask them a yes or no? How does that help anyone determine anything? The patient might have a completely wrong belief about what PEM is, and this will do nothing to identify the discrepancies.

The key thing about PEM is that it is not delayed onset muscle soreness, rapid fatiguability or anything of the sort. PEM is what you’re left with when you rule out all of the normal responses to exertion, delayed or not.

Why does this matter? Because we’ve had enough of researchers using DSQ-PEM to say that these patients had PEM when some of them very clearly did not. This will just ensure that the trend continues.

 

[Trish]

Hello, @TheDePaulGroup, Lenny Jason, thank you for joining us.

As you will have seen, I copied the questions from your questionnaire on this thread as I was filling it in, so members could discuss them.

You will also have seen that I am totally confused by the whole premise of the questionnaire, which seems to conflate the daily grind of living with ME/CFS and the episodes of PEM, the frequency and severity of which is affected by activity in the preceding days.

Your first set of questions is about symptoms we experience due to PEM.

There follows a series of symptoms, for each you are asked to answer the following 2 questions:

Frequency: Throughout the past 6 months, how often have you had this symptom due to post-exertional malaise?
0
None of the time
1
A little of the time
2
About half the time
3
Most of the time
4
All of the time

Severity: Throughout the past 6 months, when this symptom is present, how severe is it?​

0

Not present
1
Mild
2
Moderate
3
Severe
4
Very severe

The symptoms listed for which you have to answer the above 2 questions are:
Reduced stamina and/or functional capacity
Physically fatigued while mentally wired
Cognitive exhaustion
Problems thinking
Unrefreshing sleep
Insomnia
Muscle pain
Muscle weakness/instability
Aches all over your body
Dizziness
Flu-like symptoms
Temperature dysregulation
Physical fatigue

This is a list of symptoms of ME/CFS, so by definition, most of us will experience most of them most or all of the time, not just during PEM episodes.

Given that I experience almost every symptom on the list all the time, how am I supposed to answer this? Do I pick the few that I only get during PEM episodes, and say I don't get the others 'due to PEM'. But that's not right because I have them during PEM also.

And the severity question makes no sense either. If I have reduced stamina, does severe mean I can no longer work, or does it mean I'm bedbound? You need to give benchmarks if the data is to mean anything. Otherwise, why ask about severity?

The second set of questions was even more confusing:

Question 21 of 43
You will now be presented with a series of Post-Exertional Malaise case definitions. For each one please rate how often (frequency) and how intensely (severity) you have experienced this symptom over the past 6 months.

For each, you are asked these 2 questions:

Frequency: Throughout the past 6 months, how often have you had this symptom?​

0
None of the time
1
A little of the time
2
About half the time
3
Most of the time
4
All of the time

Severity: Throughout the past 6 months, when this symptom is present, how severe is it?​

0

Not present
1
Mild
2
Moderate
3
Severe
4
Very severe

Symptoms for which you are asked to answer the above 2 questions:

Next day soreness or fatigue after non-strenuous, everyday activities
Mentally tired after the slightest effort
Physically drained or sick after mild activity
Dead, heavy feeling after starting to exercise
You can interpret the word exercise as any daily activity you do such as even walking around in your house.
Minimum exercise makes you physically tired
You can interpret the word exercise as any daily activity you do such as even walking around in your house.

You describe each of the statements asked about as 'a series of PEM case definiitions'. They are no such thing, at least not in any definition I've seen, or in my experience. They are descriptions of fatigability which for many if not all pwME is part of what ME/CFS is. I experience all of them all the time during and after every activity.

I think the problem I and others are having with this questionnaire is a fundamental difference in understanding the phenomenon of PEM. You define it as

PEM involves a worsening of symptoms after physical, cognitive, or emotional exertion.

To me, and I think many others, that sentence describes what happens to us all day every day whenever we do anything physical or cognitive.

That description is incomplete according to the definitions used by the CDC and NICE, for example, which make it clear that they are talking about the usually delayed much worse episodes we experience when we have done a bit more exertion than usual, that is usually delayed after the triggering exertion and that usually lasts for days or much longer before the episode eases.

I hope you will take the time to read the fact sheet on PEM our members produced, linked below. Can you explain to us how your questionnaire would be able to determine whether someone experiences PEM of the sort we describe, and the frequency, severity and duration of the episodes of PEM, and whether your questionnnaire can distinguish this from the daily fatiguability and symptom fluctuations with each activity we do. My experience of filling it in tells me you will learn nothing about my experience of PEM episodes from my attempts at answers.

PEM_Factsheet.pdf

 

[hotblack]

Agree that focussing on predefined activities is the wrong path. Different people of different severities with different levels of support prioritise different things.

This just isn’t an accessible questionnaire, in size or structure. I gave up on it. I believe there will be self selection in who chooses and is able to complete it.

Question 4 was a bit of wall simply because there isn’t a good answer to how long my PEM lasts available because it depends. It isn’t a set amount just like there isn’t a set amount of activity that triggers it.

The way a lot of these questions are phrased the answer is often ‘it depends’ and asking about a typical or most often occurence I don’t think would be the right approach. As it is that it depends which is the important information.

Others have raised great points on aims, data protection and overall questions so I won’t repeat them.

@TheDePaulGroup We have spent a lot of time discussing questionnaires, definitions of PEM and different people’s experiences and ways of measuring patient experiences and outcomes on the forum. I’m sure there’s valuable info for the team if they want to engage further.

 

[Kitty]

Question 4 was a bit of wall simply because there isn’t a good answer to how long my PEM lasts available because it depends. It isn’t a set amount just like there isn’t a set amount of activity that triggers it.

That's the trouble with trying to come up with in-depth data on PEM. Everything is contingent on everything else.

It's possibly most usefully compared to an injury. It's essential to develop ways to describe injuries and work out how best to treat them, of course, but beyond that it all becomes conditional. How long it takes a patient to recover depends on how old and fit they were, how badly they hurt themselves, and how well they complied with medical advice afterwards. How much they aggravate the injury if they try to do too much too soon depends on all the above, plus how much they did and what stage of the recovery curve they were at.

Trying to analyse all that would probably produce nothing that's of use in treatment or management, beyond an advisory statement such as "Further damage to the injured area may delay your recovery". People already know that.

 

[Creekside]

From the survey questions Trish posted, I'd guess that the results will be quite misleading and open to misinterpretation. I expect that two people with exactly the same ME&PEM symptoms might fill out the questionnaire quite differently, based on different personalities. One will say they have "temperature dysregulation" once a month, meaning a really strong feeling of overheating or chilling, while another person claims they have it several times a day, but they're referring to a tenth of a degree variation (and they use a medical-grade thermometer several time per hour). Without those details, I can imagine researchers imputing more relevance to the data than actually exists. So, I'm not convinced that the questionnaire is going to produce useful data.

 

[Kitty]

@TheDePaulGroup – there is one type of long term PEM study that could potentially be really useful.

That would be a simple web tool that allows newly ill people who're not severely affected, and possibly those who've been ill some time but have never been severely affected, to log their more severe PEM episodes over time. As many people as possible, anywhere in the world.

So they get prompted to complete the FUNCAP perhaps twice a year, and the only other input they need to have is to record PEM that impairs them enough that they couldn't do even half their normal activities—but only starting when they've already had it for at least three days.

They don't need to describe it, just click the calendar for that day's date. Every day until they can do most of their usual activities again. (Maybe the tool only tags the episode for inclusion when it's lasted at least five or six days, but asking people to wait that long before starting recording would be difficult. Days merge into one other when you feel like death dug up.)

Analysis of that over several years might give us some evidence of whether or not frequent episodes of long-lasting PEM reduces people's underlying function. We suspect it does, but we don't have the data. A study like that could be criticised as having any number of limitations, but it might still have some value. It's lightweight enough to be usable too.

 

[MrMagoo]

Hello all,

I am part of the team that created and deployed this survey (DSQ-PEM 2). I have been reviewing all the feedback across forums, comments online, and comments left on the survey. I would like to pass on a message from Dr. Leonard Jason:

I would like to thank the patient community for their participation in our recent surveys—one focused on criteria for measuring illness severity and burden, and the other on post-exertional malaise (PEM). More than 4,000 individuals responded to the first survey, and over 600 to the second. My team and I are deeply appreciative of this remarkable response and the thoughtful comments we received. Several participants asked how we have collaborated with patient groups on these and other efforts. Below, I provide a brief overview of this broader participatory process, followed by the rationale for doing our two most recent studies.

For more than 35 years, our group has been privileged to work closely with the patient community on a wide range of initiatives. Beginning in 1990, patients alerted us to the harm caused by the CDC’s inaccurate prevalence estimates and the stigmatizing media portrayal of ME/CFS as “Yuppie Flu.” With financial support and encouragement from the largest patient organization at that time—the CFIDS Association—we conducted a pilot study that challenged the CDC’s estimate of only 20,000 affected individuals. With these pilot data, we were able to successfully obtain NIH funding, and we carried out our community-based epidemiologic research demonstrating that ME/CFS prevalence was far higher than originally reported. The effort took our group a decade. This major shift in understanding the prevalence of ME/CFS would not have been possible without the sustained engagement and guidance of the patient community. When patients raised concerns about the stigmatizing effects of the term “chronic fatigue syndrome,” we conducted research showing that labeling indeed influenced public perceptions—validating patient experiences and supporting the use of “ME” as the preferred term. These two foundational projects were both patient-driven. More details on this early collaborative work can be found in: Jason, L.A. (2015). Ethical and diversity challenges in ecologically sensitive systems-oriented interventions. American Psychologist, 70, 762–775. PMCID: PMC4863698.

In part due to these efforts, I was later appointed Chairperson of the U.S. Research Committee of the CFS Advisory Committee, which advised the Secretary of Health and Human Services. At those meetings, patients repeatedly voiced concerns about the limitations of the Fukuda criteria used in research and clinical trials. Guided by these concerns, our team spent the next decade evaluating the adequacy of these criteria. We found that many studies using Fukuda’s definition recruited participants who did not experience PEM or cognitive impairment—core symptoms of ME/CFS. Moreover, the criteria relied on symptom “occurrence” rather than precise frequency and severity measures. Our research demonstrated that such measures failed to distinguish ME/CFS from major depressive disorder, while frequency/severity metrics could make that distinction.

Addressing our work on measuring post-exertional malaise (PEM): The original DSQ was not designed as a comprehensive PEM measure, though it included ten relevant PEM items. Rather, it was a measure of the multiple symptoms that occur among patients. Just before the pandemic, we published what we call the DSQ-PEM, a short PEM tool derived from the DSQ survey. But this brief scale did not cover key issues such as the delay of onset of symptoms and triggers for symptoms. Recognizing the need for a more complete instrument, we sought patient input through social media, inviting suggestions for additional questions and refining the measure iteratively based on feedback. Once a patient-led effort had developed the PEM questionnaire, we then posted it on my Facebook account, and 1,534 patients completed the resulting comprehensive PEM questionnaire. Details on this patient-generated measure are available in:
Holtzman, C.S., Bhatia, S., Cotler, J., & Jason, L.A. (2019). Assessment of post-exertional malaise (PEM) in patients with Myalgic Encephalomyelitis (ME) and Chronic Fatigue Syndrome (CFS): A patient-driven survey. Diagnostics, 9(1), 26. However, it is a lengthy questionnaire of 8 pages.

When the pandemic began, few validated PEM measures were available, but as we know, PEM is a key symptom of Long COVID. As there were very few PEM-validated measures at the time, Long COVID researchers worldwide adopted our brief 5-item PEM scale and the 10-item DSQ-PEM, both of which have since been translated into 28 languages. These instruments that been used in dozens of articles over the last few years. However, our comprehensive 8-page PEM questionnaire proved too lengthy and was not used by researchers. This led our group to explore whether a balanced, intermediate solution could be developed—a more current and comprehensive measure than the DSQ-PEM, yet briefer and more practical than the full 8-page version. Using data that we had already collected on the 8-page version, we just examined core PEM domains, so we were able to keep it to 2 pages. We finished this study in the summer, and it has been accepted for publication in a journal. We are now working on the page proofs, but it will be released shortly.

After finalizing this briefer version, which we now call the DSQ-PEM2, we wanted to collect new data with this briefer PEM instrument. That is the instrument that I circulated last week on my Facebook page, and the items originally had been recommended by patients when we created the more comprehensive 8-page instrument, but of course, it was briefer at just two pages, with the hope that this briefer instrument might be used by investigators, and it certainly is more comprehensive than the DSQ-PEM that has been so widely used.

I also want to acknowledge the thoughtful feedback we have received regarding this new PEM instrument, and all comments are being carefully reviewed. Some participants mentioned they would have preferred to be able to skip items, and several respondents requested more details clarifying items. Several mentioned it was difficult to differentiate a PEM occurrence from the overall ME experience, and this certainly is a difficult task to differentiate in a self-report questionnaire. While we did include a question about whether pacing was effective in reducing PEM, we did not ask for each question what it would be like if a patient were not pacing, but to do so would have doubled the number of questions on our brief 2-page questionnaire. These suggestions reflect fundamental measurement issues and reinforce that operationalizing PEM in a way that matches lived experience remains a challenging process for these types of surveys. However, self-report questionnaires do have the advantage of being less expensive than many other methods, such as two-day cardiopulmonary exercise tests.

We are immensely grateful to the more than 600 participants who completed the survey. Although this version (the DSQ-PEM-2) is less detailed than the 8-page comprehensive measure, we hope it will serve as a practical and scientifically valuable tool for future research on PEM. Fortunately, there are more PEM instruments today than when we began working on the creation of DSQ in 2009.

Warm regards,

Lenny Jason

That’s a lot of info about you.

Can you explain briefly please?

 

[TheDePaulGroup]

Hello, @TheDePaulGroup, Lenny Jason, thank you for joining us.

As you will have seen, I copied the questions from your questionnaire on this thread as I was filling it in, so members could discuss them.

You will also have seen that I am totally confused by the whole premise of the questionnaire, which seems to conflate the daily grind of living with ME/CFS and the episodes of PEM, the frequency and severity of which is affected by activity in the preceding days.

Your first set of questions is about symptoms we experience due to PEM.

There follows a series of symptoms, for each you are asked to answer the following 2 questions:

Severity: Throughout the past 6 months, when this symptom is present, how severe is it?​

This is a list of symptoms of ME/CFS, so by definition, most of us will experience most of them most or all of the time, not just during PEM episodes.

Given that I experience almost every symptom on the list all the time, how am I supposed to answer this? Do I pick the few that I only get during PEM episodes, and say I don't get the others 'due to PEM'. But that's not right because I have them during PEM also.

And the severity question makes no sense either. If I have reduced stamina, does severe mean I can no longer work, or does it mean I'm bedbound? You need to give benchmarks if the data is to mean anything. Otherwise, why ask about severity?

The second set of questions was even more confusing:

Frequency: Throughout the past 6 months, how often have you had this symptom?​

Severity: Throughout the past 6 months, when this symptom is present, how severe is it?​

0


You describe each of the statements asked about as 'a series of PEM case definiitions'. They are no such thing, at least not in any definition I've seen, or in my experience. They are descriptions of fatigability which for many if not all pwME is part of what ME/CFS is. I experience all of them all the time during and after every activity.

I think the problem I and others are having with this questionnaire is a fundamental difference in understanding the phenomenon of PEM. You define it as


To me, and I think many others, that sentence describes what happens to us all day every day whenever we do anything physical or cognitive.

That description is incomplete according to the definitions used by the CDC and NICE, for example, which make it clear that they are talking about the usually delayed much worse episodes we experience when we have done a bit more exertion than usual, that is usually delayed after the triggering exertion and that usually lasts for days or much longer before the episode eases.

I hope you will take the time to read the fact sheet on PEM our members produced, linked below. Can you explain to us how your questionnaire would be able to determine whether someone experiences PEM of the sort we describe, and the frequency, severity and duration of the episodes of PEM, and whether your questionnnaire can distinguish this from the daily fatiguability and symptom fluctuations with each activity we do. My experience of filling it in tells me you will learn nothing about my experience of PEM episodes from my attempts at answers.

PEM_Factsheet.pdf

Hi Trish:

Defining PEM is certainly a challenging task, and we appreciate your comments and those of your colleagues on this forum. I believe that tracking patients’ behavior over time in combination with self-report data is the best way to understand PEM. I had written a grant with several British colleagues this past year that tried to do a PEM study that involved tracking activities with FitBit activity tracker (to collect what is called time series data) and relating that to patient reports, but unfortunately it was not funded. I think that type of naturalistic research over time, which would identify the naturalistic and cumulative triggers as well as the consequences, and is needed but unfortunately it is expensive to collect and analyze these types of data. Without that type of data, we need to rely on other ways to try to measure PEM, but each approach has its limitations.

In our study, we were doing all we could to reduce the text and the burden of time to read and complete our 8 plus page comprehensive PEM questionnaire. In other words, one of the main goals of our study was to reduce the 8 plus page former questionnaire (see Holtzman et al., 2019 for more details on this point) to 2 pages, which we thought might be helpful to other investigators and patients. Our longer 8 plus page PEM questionnaire has not achieved the visibility or use of our briefer one- and two-page DSQ-PEM surveys, which are now used around the world. But those briefer PEM items were developed over 15 years ago, and multiple domains were not assessed by our two brief DSQ-PEM measures, such as delay in symptoms and types of triggers. So, we have tried to develop an instrument that is more comprehensive than the DSQ-PEM, but much briefer than the 8 plus page comprehensive PEM instrument. To get the survey to 2 pages, we had to provide less details throughout. Making surveys briefer has consequences of not being as detailed as one might like to be but then being too detailed and comprehensive could also be a barrier to having an instrument adopted for use.

I will quote from your note the first issue you brought up: “This is a list of symptoms of ME/CFS, so by definition, most of us will experience most of them most or all of the time, not just during PEM episodes. Given that I experience almost every symptom on the list all the time, how am I supposed to answer this? Do I pick the few that I only get during PEM episodes, and say I don't get the others 'due to PEM'. But that's not right because I have them during PEM also.”

If a patient has all of the PEM symptoms all of the time, and if the patient also were at the highest severity levels, then you are right that there would be a ceiling that such a person would not be able to score any higher on either frequency or severity after any trigger. In other words, if ME/CFS symptoms for a patient are ongoing at a very high level in terms of frequency and severity, identifying more severe PEM flares would be most difficult and potentially not possible. If this were the situation, even with a two-day cardiopulmonary exercise test, each of the patient’s symptoms would be at the highest threshold prior to the exercise challenge, so efforts to study PEM as the result of the exertion challenge would be most difficult. Any of the tests that have been developed might not be able to capture PEM with such patients, and only by studying more biological aspects might we be able to understand the effects of PEM, but it might not be possible with self-report questionnaires. However, from looking over our database, almost none of the respondents have a pattern that has the highest frequency/severity ratings for all symptoms.

You then mentioned that “And the severity question makes no sense either. If I have reduced stamina, does severe mean I can no longer work, or does it mean I'm bedbound? You need to give benchmarks if the data is to mean anything. Otherwise, why ask about severity?” We think your comments conflate symptomatology with functionality, and this has created stigma for the patient community, and let us try to explain what we mean. A patient might not be able to work but not have symptoms in a number of areas (the person might be able to have refreshing sleep). The reason the person might not be able to work could be related to cognitive confusion, which would make work very difficult to do but sleep might not be impaired. On the other hand, a person who is bedbound might have no energy but also some domains where they do not have symptoms, such as having no cognitive impairment. So, your two examples conflate indicators of functionality and the intensity of symptoms. Measuring symptoms and functionality need to be assessed as independent domains. In all medical illnesses, functionality is differentiated from symptoms. A person with cancer might have lots of pain but could be very functional and have no problems working and with family and social relations. Only in the psychiatric conditions are functionality and symptoms brought together, which I think is a mistake when this comingling occurs for people with ME/CFS, and this has led to stigma for patients with ME/CFS. Patients with ME/CFS should be treated like all medical illnesses are treated and not like what occurs to those with psychiatric conditions. So, we are measuring symptoms and their severity but not the limitations that the symptoms might be having on patients. More directions about intensity could have been provided, but the severity scale (mild, moderate, severe, very severe) that we provided are used by investigators all over the world and rather standard practice and in such studies, directions to patients are not provided.

But your major issue is contained in this paragraph: “I think the problem I and others are having with this questionnaire is a fundamental difference in understanding the phenomenon of PEM. You define it as: ‘”‘PEM involves a worsening of symptoms after physical, cognitive, or emotional exertion.’”

In our consent form, we defined PEM in this way, but it was an abbreviated version of our conception of ME/CFS. There are many questionnaires/surveys that do use this type of definition to define PEM. However, in our actual survey, we did provide what we considered our definition of PEM, and it is what we expected patients to refer to when answering our questions. At the start of our survey, in Question 1, we provide responders with our definition of PEM. “Over the past 6 months, have you experienced post-exertional malaise, which is defined as an abnormal response to minimal amounts of physical and/or cognitive exertion, with symptom severity and duration out of proportion to the initial trigger?” From our data of people with ME, 99.6% answered affirmatively to this statement, suggesting that our phrasing has high sensitivity.

So, to repeat, at the beginning of our survey, we are defining PEM as “an abnormal response to minimal amounts of physical and/or cognitive exertion, with symptom severity and duration out of proportion to the initial trigger.” In contrast, in your post, you defined PEM as “the usually delayed much worse episodes we experience when we have done a bit more exertion than usual, that is usually delayed after the triggering exertion and that usually lasts for days or much longer before the episode eases.”

These two definitions are worth examining in more detail as they are a major reason that we have differences in opinions on our definitions of PEM. There are two parts of this difference, and to summarize, you use the term “much worse episodes we experience” and “a bit more exertion than usual” whereas our group uses the terms: “an abnormal response to minimal amounts of physical and/or cognitive exertion” which is “out of proportion to the initial trigger.” So, one defines the trigger and the other defines the PEM outcome, and we will inspect both aspects of our different approaches to these issues. Regarding PEM outcome, you prefer “much worse episode” and we use the term “abnormal response”, and both try to capture the phenomena. In your PEM definition, you use the term “much worse episodes” to differentiates the current symptoms from what have been experienced previously. We have some concerns with these types of phrases using terms such as worse in a comparison capacity. The use of words such as “much worse” reminds us of the controversy regarding Chalder et al.’s (1993) fatigue scale, whose responses were rated on a four-option continuum ranging from 0 = less/better than usual to 3 = much more/much worse than usual. For patients that have been sick for many years, unfortunately, it is unclear what it means to have symptoms that are “worse than usual”. The Chalder Fatigue Scale has not demonstrated efficacy in discriminating between different subtypes of individuals with fatigue, and it has not demonstrated an ability to distinguish individuals with ME/CFS from those with primary depression (Friedberg & Jason, 1998). We might mention that the Chalder group and their scales were used by the British investigators who popularized CBT for patients with ME/CFS.

Now we examine the differences in the trigger phrases for our definitions of PEM. Our group would argue that there are some benefits of our PEM definition of “an abnormal response” to exertion that is out of proportion to the trigger, which is a marker that would signify to the patient that a PEM experience has occurred. In other words, you define the trigger as “a bit more exertion than usual” whereas we define it as “minimal amounts of physical and/or cognitive exertion with symptom severity and duration out of proportion to the initial trigger”. One could debate which is more accurate. In the article by Holtzman et al. (2019), when describing PEM triggers, 78.2% endorsed “basic activities of daily living”, 64.5% endorsed “positional changes”, and 93.2% endorsed “emotional stress (good or bad)”. Additionally, 84.9% said there were some instances in which the specific precipitants could not be identified.” So, there will be times when PEM occurs where it is unclear what your “a bit more exertion than usual” would refer to. In other words, it could be argued that some patients might not be clear with what you refer to as “a bit more exertion than usual”. If severely affected, it might not be clear what is more than usual. For example, it might not be more exertion that precipitates PEM but usual amounts of exertion in addition to other triggering events, such as positional changes. This gets into the complexity of defining PEM. If bedbound, and if PEM occurred with no exertion, but some other triggering event such as bright light, would such a person also not have PEM according to your definition. What if the person’s baseline symptoms are so intense that “more than usual” is no longer something the person can understand and would such a person also be excluded as not being able to have PEM. I am just suggesting that what is “usual” is not an easy concept to understand for a person who has lost that ability to have what is called a “usual” baseline. So, when we refer to symptom and duration out of proportion to the trigger, our phrasing trigger might be more flexible and accurate than your use definition which uses the term “usual”.

Finally, by your definition stating that the duration of PEM usually lasts for days or longer, there might be unintentional, but scientific bias introduced to a survey trying to assess PEM. For many patients, the PEM does not last for days or longer and in our database, we did identify those whose PEM occurred for 24 or less hours. It could be that for some, pacing and carefully observing their activity could limit PEM to less than 24 hours. In contract, our definition of “duration out of proportion to the initial trigger” does not define the period of time, and that way a respondent is not given an expectation of how long the PEM should last, which if stated and defined as you have could even unintentionally bias the results of an investigation by suggesting to the respondent of how long PEM might last.

Many also mentioned concerns about providing information such as racial background or education history. We understand your caution regarding data protection and privacy. However, nearly all academic journals and ethics committees require basic demographic information in studies involving human participants. This helps ensure transparency and allows other researchers to interpret the generalizability of findings (for example, whether results differ by gender, age, or education). This survey was anonymous, and these demographic data are analyzed only in aggregate. No identifying information is ever collected or reported, and the data are used solely for scientific purposes in compliance with data protection standards, including GDPR.

We thank you for the time in dialoguing with us, and hope that our responses provide you and others with at least our effort to respond to your questions about our research.

The references to the articles referred to in our text are below:

Chalder, T., Berelowitz, G., Pawlikowsy, J., Watts, L. & Wessely, D. (1993). Development of a fatigue scale. Journal of Psychosomatic Research, 37, 147-153.

Friedberg, F. & Jason, L.A. (1998). Understanding chronic fatigue syndrome: An empirical guide to assessment and treatment. Washington, D.C.: American Psychological Association.

Holtzman, C.S., Bhatia, S., Cotler, J., & Jason, L.A. (2019). Assessment of post-exertional malaise (PEM) in patients with Myalgic Encephalomyelitis (ME) and Chronic Fatigue Syndrome (CFS): A patient-driven survey. Diagnostics, 9(1), 26. https://doi.org/10.3390/diagnostics9010026

 

[Mij]

The delayed PEM feels like a different illness for me symptom-wise. It is severe if I exceed my energy limit. Otherwise I would consider myself mild/moderate when describing symptoms which I don't have many, but I am mostly housebound and disabled.

 

[Peter T]

Defining PEM is certainly a challenging task, and we appreciate your comments and those of your colleagues on this forum. I believe that tracking patients’ behavior over time in combination with self-report data is the best way to understand PEM. I had written a grant with several British colleagues this past year that tried to do a PEM study that involved tracking activities with FitBit activity tracker (to collect what is called time series data) and relating that to patient reports, but unfortunately it was not funded. I think that type of naturalistic research over time, which would identify the naturalistic and cumulative triggers as well as the consequences, and is needed but unfortunately it is expensive to collect and analyze these types of data.

Such a shame you did not get funding for this study. I feel it would be very useful in the absence of an understanding of ME’s aetiology to have a good quantitative as well as qualitative description of symptom variation between and within individuals.

 

[Sly Saint]

This just isn’t an accessible questionnaire, in size or structure. I gave up on it. I believe there will be self selection in who chooses and is able to complete it.

this

 

[Utsikt]

So, we are measuring symptoms and their severity but not the limitations that the symptoms might be having on patients.

Then you’re not measuring PEM! PEM is not just symptoms, it’s also functional impairment causes by additional symptoms and functional impairment caused by the threshold for more PEM being substantially decreased.

You can’t call it a PEM questionnaire if you’re only measuring half of it.

These two definitions are worth examining in more detail as they are a major reason that we have differences in opinions on our definitions of PEM. There are two parts of this difference, and to summarize, you use the term “much worse episodes we experience” and “a bit more exertion than usual” whereas our group uses the terms: “an abnormal response to minimal amounts of physical and/or cognitive exertion” which is “out of proportion to the initial trigger.

For patients that have been sick for many years, unfortunately, it is unclear what it means to have symptoms that are “worse than usual”.

I think this has a very easy solution: define what you mean by usual. I think it’s very clear that «usual» in the context of PEM means «your usual symptoms when accounting for your disease».

And your «abnormal» has the exact same issue - abnormal compared to which reference?

Edited this section for clarity.

From our data of people with ME, 99.6% answered affirmatively to this statement, suggesting that our phrasing has high sensitivity.

That’s circular. Everyone with an ME/CFS diagnosis will answer yes if you ask if they have PEM, regardless of how you define it. That’s the issue with your survey here - it’s essentially saying that «you have PEM because you said you have PEM», not «you have PEM because the patterns of symptoms you described to us matches how we define PEM».

Edit: I know the survey provides a definition of PEM, but lets not kid ourselves; people don’t pay that much attention to that kind of stuff. They see «PEM» and click yes. So in practice, it becomes circular. Even the name of the survey risks making it circular.

In other words, you define the trigger as “a bit more exertion than usual” whereas we define it as “minimal amounts of physical and/or cognitive exertion with symptom severity and duration out of proportion to the initial trigger”.

Say you’re bedbound and you rarely use your hands fine motor skill tasks. Due to severe deconditioning of your hands and lower arms, when you try to write with a pen your lower arm muscles start spasming for hours.

Is that PEM according to your definition?

Finally, by your definition stating that the duration of PEM usually lasts for days or longer, there might be unintentional, but scientific bias introduced to a survey trying to assess PEM. For many patients, the PEM does not last for days or longer and in our database, we did identify those whose PEM occurred for 24 or less hours. It could be that for some, pacing and carefully observing their activity could limit PEM to less than 24 hours. In contract, our definition of “duration out of proportion to the initial trigger” does not define the period of time, and that way a respondent is not given an expectation of how long the PEM should last, which if stated and defined as you have could even unintentionally bias the results of an investigation by suggesting to the respondent of how long PEM might last.

By not setting a lower cutoff you’re essentially allowing for everything that might not have anything to do with PEM and just be due to deconditioning.

I also don’t understand how the results could be biased because the purpose of the questionnaire is to identify PEM, not any symptom experienced ever. So it becomes circular again: symptoms are PEM if the patient says they are PEM, not because they meet the requirements of being PEM.

 

[StellariaGraminea]

Just catching up on this thread. I filled out this survey questionnaire and found it v. confusing as others have pointed out. I had the same issues. The initial description sounds like it could cover "exercise intolerance" for other reasons (e.g. cardiovascular diagnosis) separate from PEM. As someone with LC related ME and also cardiovascular related issues as part of LC this definition seems like a problem.

I appreciate PEM is a slippery thing to pin down in a questionnaire & especially this one for all the reasons described so well by others here. I also found I needed a benchmark to anchor my interpretation of severity level (I think it was Trish pointed this out). I have been much more severe previously and am never sure now whether to tick "mild" or "moderate" for a symptom. If I compare to where I was before "mild" is correct. If I compare to my healthy self before this illness I would still be ticking "severe" on quite a number of things. So I just threw my hands in the air (metaphorically) answering this questionnaire because I felt clueless re which severity would be an accurate one to tick.

Also, I've had a step improvement within the last 6 months. So the "answer for the last 6 months" idea is problematic. Averaging would not represent where I was at any time point, but do I select the more severe time before the step improvement, or do I just go on the more recent improved level? I've no idea.

I really felt my responses on this questionnaire were meaningless. As someone said, a lot of them I needed an "it depends" to explain. In the absence of that I can imagine someone else misinterpreting the responses I chose to mean something I didn't intend.

It's a real pity that the qualitative study wasn't funded.

 

[Yann04]

Then you’re not measuring PEM! PEM is not just symptoms, it’s also functional impairment causes by additional symptoms and functional impairment caused by the threshold for more PEM being substantially decreased.

You can’t call it a PEM questionnaire if you’re only measuring half of it.


I think this has a very easy solution: define what you mean by usual. I think it’s very clear that «usual» in the context of PEM means «your usual symptoms when accounting for your disease».

Chalder compares to before you got sick, which is obviously an issue.

And your «abnormal» has the exact same issue - abnormal compared to which reference?

That’s circular. Everyone with an ME/CFS diagnosis will answer yes if you ask if they have PEM, regardless of how you define it. That’s the issue with your survey here - it’s essentially saying that «you have PEM because you said you have PEM», not «you have PEM because the patterns of symptoms you described to us matches how we define PEM».

Say you’re bedbound and you rarely use your hands fine motor skill tasks. Due to severe deconditioning of your hands and lower arms, when you try to write with a pen your lower arm muscles start spasming for hours.

Is that PEM according to your definition?

By not setting a lower cutoff you’re essentially allowing for everything that might not have anything to do with PEM and just be due to deconditioning.

I also don’t understand how the results could be biased because the purpose of the questionnaire is to identify PEM, not any symptom experienced ever. So it becomes circular again: symptoms are PEM if the patient says they are PEM, not because they meet the requirements of being PEM.

I hate to say it but I agree on every point here.
I think this survey unfortunately is unfit for purpose. It may still yield some useful data, but not what was trying to be measured.

I’m very grateful the team is engaging with us in this thread. And I’m very grateful for the continuous work into ME/CFS. But I think survey design has to be rethought here.

I’d encourage the team to engage with us earlier on in the process of designing future surveys. A lot of people here have an astute and critical eye which could yield useful observations for researchers creating a survey.

 

[Trish]

But your major issue is contained in this paragraph: “I think the problem I and others are having with this questionnaire is a fundamental difference in understanding the phenomenon of PEM. You define it as: ‘”‘PEM involves a worsening of symptoms after physical, cognitive, or emotional exertion.’”

In our consent form, we defined PEM in this way, but it was an abbreviated version of our conception of ME/CFS. There are many questionnaires/surveys that do use this type of definition to define PEM. However, in our actual survey, we did provide what we considered our definition of PEM, and it is what we expected patients to refer to when answering our questions. At the start of our survey, in Question 1, we provide responders with our definition of PEM. “Over the past 6 months, have you experienced post-exertional malaise, which is defined as an abnormal response to minimal amounts of physical and/or cognitive exertion, with symptom severity and duration out of proportion to the initial trigger?”

So, to repeat, at the beginning of our survey, we are defining PEM as “an abnormal response to minimal amounts of physical and/or cognitive exertion, with symptom severity and duration out of proportion to the initial trigger.” In contrast, in your post, you defined PEM as “the usually delayed much worse episodes we experience when we have done a bit more exertion than usual, that is usually delayed after the triggering exertion and that usually lasts for days or much longer before the episode eases.”

These two definitions are worth examining in more detail as they are a major reason that we have differences in opinions on our definitions of PEM. There are two parts of this difference, and to summarize, you use the term “much worse episodes we experience” and “a bit more exertion than usual” whereas our group uses the terms: “an abnormal response to minimal amounts of physical and/or cognitive exertion” which is “out of proportion to the initial trigger.” So, one defines the trigger and the other defines the PEM outcome, and we will inspect both aspects of our different approaches to these issues. Regarding PEM outcome, you prefer “much worse episode” and we use the term “abnormal response”, and both try to capture the phenomena. In your PEM definition, you use the term “much worse episodes” to differentiates the current symptoms from what have been experienced previously. We have some concerns with these types of phrases using terms such as worse in a comparison capacity.

I don't have the capacity to respond to all of your feedback on my comment tonight, I just want to respond to the above for now.

I agree I described PEM rather loosely, saying 'a bit more than usual'. That was not intended to be a formal definition, rather to point to the fact that your definition focuses on increased symptoms, but I was trying to say a lot of us experience increased symptoms with every activity. Just lying in bed typing this I feel my muscles getting more and more painful, and I my error rate is increasing and speed decreasing as I type due to cognitive and physical fatiguability, but that's not PEM in my understanding, it's the daily experience of ME/CFS. Provided I don't do too much overall today, I will probably be able to do more posting on the forum tomorrow, ie I won't have triggered PEM. If I have triggered PEM by today's activities, I will be unable to participate on the forum, probably feel too nauseous to eat, and need to lie quietly in the dark.

I asked you to read our fact sheet about PEM.
https://www.s4me.info/threads/science-for-me-fact-sheets.43310/post-606969
Note that the factsheet is written in plain English, avoiding medical terminology as it's intended to be accessible for all, from new patients to clinicians.

Here's what we say about the key characteristics of PEM

Characteristics of PEM

People with ME/CFS experience episodes when they are much more ill and cannot do as much as usual following amounts of physical or mental exertion or sensory stimuli that they could easily tolerate before the illness. This is called post-exertional malaise, or PEM. PEM is the hallmark of ME/CFS and important for diagnosis.

The main features of an episode of PEM are:

• A person feels more ill. Their usual symptoms get much worse, and new symptoms may appear.
• They are much less able to function. They need to rest more, or even to lie still in silence and darkness, until it passes.
• The onset of PEM is typically delayed for hours or up to several days after it is triggered.
• The length and severity of an episode of PEM are out of proportion to the amount of exertion or stimulus that triggered it. An episode can last hours, but more often lasts days, weeks or longer.

Comparing the above with your definition, we include all the points in your definition in our key characteristics, but we also include delay, duration and significant reduction in function.

Your definition doesn't mention loss of function during PEM episodes, and your questions are all focused on symptoms which are part of ME/CFS all the time, not just during PEM.
Your definition

“Over the past 6 months, have you experienced post-exertional malaise, which is defined as an abnormal response to minimal amounts of physical and/or cognitive exertion, with symptom severity and duration out of proportion to the initial trigger?”

So I have a simple question for you. Do you agree with our list of the key characteristics of PEM, including the reduction in function?

If so, then why haven't you included it in the quetsionnaire? If not, then we have a very different view of what PEM is.

 

[Nightsong]

As there were very few PEM-validated measures at the time, Long COVID researchers worldwide adopted our brief 5-item PEM scale and the 10-item DSQ-PEM, both of which have since been translated into 28 languages. These instruments that been used in dozens of articles over the last few years.

Indeed; but, most unfortunately, this has not been to our benefit. A few brief examples:

1/ From the Nerli et al paper (link) on their "transdiagnostic rehabiliation" programme:

Generally, there was a tendency toward stronger beneficial intervention effects among the subgroup with the highest PEM scores at baseline and those fulfilling PIFS criteria where PEM was regarded as a hallmark of PIFS.

Based on the present results, which also showed an overall significant decrease in PEM in the intervention group, it does not seem relevant to take PIFS diagnosis or the presence of PEM into account when developing an individualized rehabilitation plan. This notion fits well with another study showing that exercise is well tolerated independent of PEM in patients with PCC.

That is entirely implausible if these patients genuinely had PEM; if they "crashed", as I do, from trivial levels of physical exertion.

2/ From the RECOVER-Adult study (link):

The most common symptoms in participants with likely LC were fatigue (85.8% [2002/2334]), postexertional malaise (87.4% [2041/2334]), postexertional soreness (75.0% [225/300]), dizziness (65.8% [1535/2334]), brain fog (63.8% [1488/2334]), gastrointestinal symptoms (59.3% [1385/2334]), and palpitations (58.0% [1353/2334])

So more "likely LC" participants apparently had PEM than fatigue; again, that seems quite implausible, given how common fatigue is in both the general population and in post-viral cases.

3/ From the Barz et al LC exercise programme paper (link):

(a) age between 18 and 79 years, (b) confirmed SARS-CoV-2 infection (positive PCR test) ≥ 12 weeks before, (c) mild to moderate course of COVID-19, (d) presence of fatigue symptoms for ≥ 12 weeks, (e) < 1 h/week of physical exercise within the last 3 months, (f) no contraindications for physical training (pre-existing conditions, medication) and (g) a medical certificate for physical activity readiness. Exclusion criteria were a Post-COVID-19 Functional Status (PCFS)-score of 4 as this indicates an inability to perform activities of daily living and thus exercise without assistance[47] and hospitalization due to COVID-19.

The DSQ-PEM indicated PEM in all participants in CON at study onset. In INT, two participants were below the threshold for PEM at PRE. Mean PEM frequency and intensity showed overall mild to moderate PEM in CON (PEM: 2.39 ± 0.68) and INT (PEM: 2.43 ± 0.75) at study onset.

Again, it does not seem plausible that, in a patient cohort defined by such very broad criteria, all of them had PEM and that the programme itself had "no effects on PEM".

Such results - and others using DSQ-PEM and the PEM-related questions on the short-form DSQ - allowed Norway's principal psychosomatic panjandrum, Wyller, to opine last year (link) about an "increasing body of evidence confirming that physical activity is not harmful in conditions characterised by PEM" and to recommend "behavioural approaches" to treat our "functional brain aberration".

Whatever DSQ-PEM is really measuring - probably exertional intolerance - it does not adequately capture what I and others here mean by PEM.

(I was going to discuss the questionnaire itself, but don't have the capacity to write more, so will have to leave it there. There are, I think, also a few other examples of how DSQ-PEM has produced implausible-seeming results - I remember mentioning a few on paper-specific threads over time.)

 

[Peter T]

This is not intended to be an exact definition but disproportionate fatigue and or worsening of symptoms is a feature of many conditions including such as MS or stroke or even such as flue. We tend here to label this increased or more rapid fatiguability. This may overlap with such labels as exertion intolerance and post exertion symptom exacerbation. This also can occur in ME/CFS and some, I would argue mistakenly, describe this as PEM. This increased fatigue or worsening of symptoms may rapidly abate once the trigger activity is stopped and/or rest is initiated.

For me PEM is in some sense a change of state, it includes increased fatiguability, but also includes features not a feature of normal or even enhanced fatigue. PEM involves increased symptoms but also potentially new symptoms, may be delayed, may paradoxically go on worsening over hours or days or even longer after onset despite ongoing rest, involves a sense of feeling ill, perhaps swollen glands, etc. Also other issues such as sensory hypersensitivities or orthostatic intolerance may be triggered more easily, and the threshold for further PEM is lowered, introducing the possibility of rolling PEM in the more severe. This state may prove to be unique to ME/CFS. Over time the actual symptoms involved with PEM may change or evolve.