Is the NIH/CDC going to use the right PEM definition for all their future research? Do patients need to act? Deadline 31 Jan

me too. Another reason to be careful not to be too prescriptive?

 

Agreed. However the apparent existence of PEM in other conditions could be due to inadequate assessment tools (questionnaires). Not long ago there was a repeated CPET PEM paper where ME/CFS and MS were clearly separated on the basis of the 2nd day CPET results (that's how I remember it anyway). I'm pretty sure that if questionnaires are used, the apparent prevalence of PEM would be higher among MS patients. Then again the 2 day CPET might be measuring only one aspect of PEM.

There are probably also a substantial number of people with ME/CFS who were incorrectly diagnosed with some other disease.

 

I haven't read all the responses, sorry. Currently only a week past an exhausting experience, so ironically I am still too deep in PEM for much reading.
My contribution:
I think it is essential that any measure stands up in terms of specificity.
Many health conditions include fatigue that is worsened by effort, but it is not qualitatively the same as PEM.

From my own experience with Lyme and that of people close to me with cancer, there are three key differences to me.
Firstly, delayed onset does not seem to be usual in other fatiguing conditions.
Secondly, in other conditions rest seems to provide a predictable and fairly rapid recovery path.
Thirdly, in other conditions physical activity seems to result in physical fatigue; cognitive effort to result in cognitive fatigue; emotional effort to result in emotional fatigue. (For me, this included flu-like symptoms with Lyme, in response to physical effort.) To me, it seems likely that, for example, disabling physical symptoms in response to cognitive activity might be specific to ME.

I find it hard in some ways to describe the difference between my body's response to too much exertion with Lyme and my experience of PEM, but it was clearly different for me. I think we need to be able to capture that.

 

[/QUOTE] The danger is we start defining PEM as “whatever it is that separates us from every other diseases” rather than focusing on what are the common experiences of patients with this illness in response to exertion. The fact that the " spoonie" idea is so popular suggests our issue may not be unique. I think it genuinely needs more work to explore that, but that shouldn’t stop us making sure that the N I H/CDC define our experience accurately.[/QUOTE]

 

I very much appreciate all the thought given to trying to describe PEM, and as is evident, this is a challenging task, and our group has been dealing with these issues for many years, using quantitative, qualitative and mixed method approaches. I generally do not post my thoughts on these sites, but thought this time, it might be useful to do so. At the end of this post, we provide references to some of our work in this area, and how those publications can be accessed for those that want more details of our path. We do have many other articles that deal with PEM, but this is a sample of the types of work our group has been doing, some of it dating back to the mid-1990s. Certainly, getting feedback is helpful, and we think that continuing efforts to define this critical symptom is important for the field.


Madison Sunnquist and I have read through the thread, and it seems like there are 2 main categories of criticism regarding our work:



Critique 1: The DSQ symptoms don’t reflect their experiences of PEM (e.g., PEM might involve flu-like symptoms, as opposed to muscle soreness or fatigue; some individuals focused on the delayed onset feature of PEM, though we do have an item that mentions ‘next day’ soreness). Even though each individual symptom might not reflect the varied presentations of PEM, in our large sample (>1,000 individuals with ME), 95.4% reported PEM (ie, had at least one of the symptoms at a frequency/severity >=2), so it does appear that, overall, we’re capturing most individuals in our samples. Additionally, in our DSQ 2.0 (which we have been working on for the past year), we’ll be adding the following symptom (based upon one of our study’s participatory PEM research) that seems to be more consistent with many of the suggestions we saw in the threads: “Worsening of symptoms after mild activity.” According to one of our RA’s work, 93.8% of our participants with ME endorsed this symptom (f/s>=2/2), but almost all of these individuals had also endorsed one of our original PEM items as well.



Critique 2: Individuals might not experience PEM if they pace. This is a good point, and have considered treating our PEM items in a similar manner to how we changed our alcohol intolerance item. For example, we could preface the statements with, “If you were to engage in activity…” Despite this critique, as we mentioned above, most participants still report significant PEM; our thought is that this is due to the 6-month timeframe (it seems like it would be exceptionally difficult to pace consistently for half of a year).

If you go to this site: https://www.researchgate.net/ then, do a search on my name (Leonard A. Jason) and when you get to my cite, request full text of any of the articles below, and I can send you via researchgate a private copy.


McManimen, S. L., Sunnquist, M. L., & Jason, L. A. (in press). Deconstructing post-exertional malaise: An exploratory factor analysis. Journal of Health Psychology, 1-11. Published online August 25, 2016. doi: 10.1177/1359105316664139
Post-exertional malaise is a cardinal symptom of myalgic encephalomyelitis and chronic fatigue syndrome. There are two differing focuses when defining post-exertional malaise: a generalized, full-body fatigue and a muscle-specific fatigue. This study aimed to discern whether post-exertional malaise is a unified construct or whether it is composed of two smaller constructs, muscle fatigue and generalized fatigue. An exploratory factor analysis was conducted on several symptoms that assess post-exertional malaise. The results suggest that post-exertional malaise is composed of two empirically different experiences, one for generalized fatigue and one for muscle-specific fatigue.


McManimen, S. L., & Jason, L. A. (2017). Post-exertional malaise in patients with ME and CFS with comorbid Fibromyalgia. SRL Neurology & Neurosurgery, 3, 22-27. PMCID: PMC5464757
Myalgic Encephalomyelitis (ME) and Chronic Fatigue Syndrome (CFS) share some similar symptoms with Fibromyalgia (FM). Prior research has found increased illness severity when patients have FM that is comorbid with ME and CFS. For example, Post- Exertional Malaise (PEM) has been shown to be more severe in those with comorbid FM. However, PEM can be separated into two factors, Muscle and General PEM. It is unknown if the more severe PEM findings in comorbid FM are due to the Muscle or General PEM factor. The purpose of this study was to determine if the PEM differences seen between patients with and without comorbid FM exist for the Muscle or General PEM factors. An international convenience sample was collected via an online questionnaire. The questionnaire assessed the frequency and severity of several PEM-related symptoms. Additionally, participants provided information regarding the course and characteristics of their illness. Participants that indicated a comorbid diagnosis of FM displayed significantly more frequent and severe PEM symptoms in the Muscle and General PEM factors. The FM group also indicated significantly worse physical functioning compared to the group without comorbid FM. The secondary diagnosis of FM in addition to ME and CFS appears to amplify the PEM symptomatology and worsen patients’ physical functioning. The findings of this study have notable implications on the inclusion of patients with comorbid FM in ME and CFS research studies.

Jason, L.A., Ohanian, D., Brown, A., Sunnquist, M., McManimen, S., Klebek, L., Fox, P., & Sorenson, M. (2017). Differentiating Multiple Sclerosis from Myalgic Encephalomyelitis and Chronic Fatigue Syndrome. Insights in Biomedicine, 2, No. 2: 11. doi: 10.21767/2572-5610.100011
Multiple Sclerosis (MS), Myalgic Encephalomyelitis (ME), and Chronic Fatigue syndrome are debilitating chronic illnesses, with some overlapping symptoms. However, few studies have compared and contrasted symptom and disability profiles for these illnesses for the purpose of further differentiating them. The current study was an online self-report survey that compared symptoms from a sample of individuals with MS (N = 120) with a sample of individuals with ME or CFS (N = 269). Respondents completed the self-report DePaul Symptom Questionnaire. Those individuals with ME or CFS reported significantly more functional limitations and significantly more severe symptoms (for fatigue, post-exertional malaise items, sleep items, pain items, neurocognitive items, autonomic items, neuroendocrine items, and immune items) than those with MS. The implications of these findings are discussed.


Jason, L.A., Evans, M., So, S., Scott, J., & Brown, A. (2015). Problems in defining post-exertional malaise. Journal of Prevention and Intervention in the Community, 43(1), 20-31. doi: 10.1080/10852352.2014.973239
PMCID: PMC4295644
Post-Exertional Malaise (PEM) is a cardinal symptom of the illnesses referred to as Myalgic Encephalomyelitis (ME), Myalgic Encephalomyelitis/chronic fatigue syndrome (ME/CFS), and chronic fatigue syndrome (CFS). PEM is reported to occur in many of these patients, and with several criteria (e.g., ME and ME/CFS), this symptom is mandatory (Carruthers et al., 2003, 2011). In the present study, 32 participants diagnosed with CFS (Fukuda et al., 1994) were examined on their responses to self-report items that were developed to capture the characteristics and patterns of PEM. As shown in the results, the slight differences in wording for various items may affect whether one is determined to have PEM according to currently used self-report criteria to assess CFS. Better understanding of how this symptom is assessed might help improve the diagnostic reliability and validity of ME, ME/CFS, and CFS.


Jason, L.A., & Evans, M. (2012). To PEM or not to PEM? That is the question for case definition. Research 1st Retrieved May 2, 2012 at: http://www.research1st.com/2012/04/27/pem-case-def/
The criteria for defining cases is an important topic in research and medicine. For chronic fatigue syndrome, it has been a vexing topic whether one considers CFS to be a new condition identified with the 1988 case definition (Holmes, et al.) or a new (if unwanted) name for a condition that has existed for decades, if not centuries, by other names. Here we will examine the cluster of symptoms known as post-exertional malaise (PEM) and its importance in defining the condition. PEM is also known as post-exertional relapse. It refers to the aggravation of various symptoms following even modest physical or mental exertion.


Jason, L.A., Sunnquist, M., Brown, A., Furst, J., Cid, M., Farietta, J., Kot, B., Bloomer, C., Nicholson, L., Williams, Y., Jantke, R., Newton, J.L., & Strand, E.B. (2015). Factor analysis of the DePaul Symptom Questionnaire: Identifying core domains. Journal of Neurology and Neurobiology, 1(4). doi http://dx.doi. org/10.16966/2379-7150.114 PMCID: PMC4830389
The present study attempted to identify critical symptom domains of individuals with Myalgic Encephalomyelitis (ME) and chronic fatigue syndrome (CFS). Using patient and control samples collected in the United States, Great Britain, and Norway, exploratory factor analysis (EFA) was used to establish the underlying factor structure of ME and CFS symptoms. The EFA suggested a four-factor solution: post-exertional malaise, cognitive dysfunction, sleep difficulties, and a combined factor consisting of neuroendocrine, autonomic, and immune dysfunction symptoms. The use of empirical methods could help better understand the fundamental symptom domains of this illness.


Jason, L.A., Jessen, T., Porter, N., Boulton, A., Njoku, M.G., & Friedberg, F. (2009). Examining types of fatigue among individuals with ME/CFS. Disability Studies Quarterly, 29, (available at http://www.dsq-sds.org/article/view/938/1113).

Severe, persisting fatigue is a prominent symptom of Myalgic Encephalomyelitis/chronic fatigue syndrome (ME/CFS), but individuals with this illness frequently report the occurrence of unique fatigue states that might be different from conventional symptoms of fatigue. The present study attempted to assess a comprehensive set of fatigue symptoms that have been commonly reported among patients with ME/CFS. A 22-item fatigue questionnaire was developed and administered to 130 persons diagnosed with ME/CFS and 251 controls. Adequate scale reliability was found. Factor analyses revealed a five-factor structure for participants with ME/CFS but only a one factor solution for the control group. The new scale was also contrasted with other more traditional scales developed to measure fatigue. Findings suggest that individuals with ME/CFS experience different types of fatigue than what are reported in the general populations.

 

Could I ask for feedback on the following:

The core PEM instrument that was recommended uses the DSQ PEM questions as the first step but also includes a second step by the researcher/clinician which is intended to identify those cases that might falsely indicate the presence or absence of PEM. For instance, if a person is working two jobs and going to school, he could conceivably respond in a way that suggests PEM. On the other hand, it a patient is pacing, then that person could look like they dont have PEM.

Page 9 of the PEM CDE document contains the second page of the CRF with the rest of the questions. Question 8 is used to capture whether PEM exists or not based on this two step process. The directions for this 2 step process, on Page 10, are:

The standard method for evaluating the “Global PEM Determination” is a two step process in which the study participant responds to the DSQ PEM questions and the researcher than evaluates those responses in light of other information about the study participant to determine whether the study participant has PEM or not. In making this determination, the researcher or clinician will need to consider whether there are other conditions, such as overwork, that could result in a false positive DSQ PEM subscale response. On the other hand, the researcher or clinician should also consider whether the study participant responded negatively because, for instance, they carefully manage their energy expenditures with pacing to avoid episodes of PEM. In addition to asking questions about workload and pacing, the researcher may also ask what happens to the study participant if/when they engage in physical or mental activity and whether there are activities they avoid because it exacerbates symptoms. ​

Does this address the concern above about missing PEM because of pacing? Is there something else/different that needs to be done?

Thank you for the feedback
Mary

 

Hi @Medfeb.

Because of our experiences here in the UK some of us are wary of having our words twisted, interpreted or misinterpreted.

In questionnaires here questions have been worded to elicit responses that can then be interpreted in a certain way i.e. to indicate depression or anxiety where there is none.

I no longer fill in questionnaires that contain questions that are in any way ambiguous or where the answers might be open to interpretation, because this has been used against me in the past.

If it is not clear cut and if it allows for someone else to "interpret" answers, I won't fill it in.

 

I'm afraid I don't have the concentration to read the documents at present, but wish to emphasise that in some people PEM doesn't occur until more than a day after activity, i.e. up to 48 hours after.

 

Welcome to the forum, @Leonard Jason, and thanks very much for contributing to the discussion. I'm very grateful for your research work over the years and I think this PEM issue is an important one.

I think the two key issues that @Simon raised remain, though. The first is that there was a lot of 'Yes, that's it! That's PEM!' from patients when the IOM report came out in 2015 with its list of features summarising PEM - and that that list is very different from the one on the DePaul subscale, which has had everyone who has contributed to this thread saying, 'No, that's not me. I don't recognise that.'

The second issue is this crucial one that the frequency and intensity of a patient's PEM is going to depend on how hard they push themselves, so having a rating scale based on frequency and intensity of PEM isn't saying anything useful about PEM and may even miss patients who have it if they're able to pace themselves to avoid it.

You wouldn't be human if it didn't sting a bit to have put all this work into your PEM scale and then have patients say, 'But that's not PEM!' and I'm sorry to be critical of the scale. I hope we don't sound ungrateful. But I think that we're at the beginning of a research process with this particular symptom. It's so far out of most people's experience and it's taken a lot of discussion over many years even for patients to get any clarity on what is meant by it.

For some symptoms in medicine, we just don't have the language and that has caused us a lot of problems in dealing with PEM.

 

I hoped I'd flagged up the first point in my initial thread post. I understand that overwork word normally stop any physician going down the route of considering ME until it had been addressed. As for pacing, certainly the 2-step helps, but my concern (and that of others) was that the patient doesn't have the chance to respond properly to the questions: we need questions that don't need interpreting. It would be better to give patients the chance to give more relevant answers, and that would ease the burden on researchers too.

Welcome @Leonard Jason and thanks for being willing to engage in the discussion with such a considered response. I agree that this is not an easy symptom to pin down. I will be responding to your post later but have very limited energy and want to look up a couple of things first.

 

It doesn't. People with other chronically fatiguing syndromes such as post-polio, GBS, Lupus etc also suffer PEM like symptoms.

There is one objective sign that cannot be faked, namely a reduction in ventilatory threshold on the 2 day maximum exercise test (CPET), the problem is this test isn't really suitable for most people with chronic illness.

 

Thanks @Simon M

Edit:
The CDEs are due to go live in the March timeframe -at least I think that's the timing - and can start to be used right away. Any thoughts on what we should do in the short term - until that more sophisticated instrument is developed and evaluated - to ensure a common approach to assessing the presence or absence of PEM?

If you can, it would be really helpful to get your feedback/recommendations on how this should be done in the short term/first release and then also feedback/recommendation on what is needed going forward.

 

.

I agree with this too.

For me, I always have ME symptoms but PEM flares everything up even worse and takes time and rest to ease again and that time frame can be different each time.

I wish I could have been tested in my severe years because PEM was so extreme in those years and those hits were hard hitting PEMs, on top of already brutal symptoms. I am still very disabled but PEMs are not as bad as they once were, I guess because I rest all afternoon and evening to try and stop deterioration back to a severe level.

 

For my daughter PEM kicks in significantly at 48-72 hours. Next day is " tired and sore"
PEM is being confined to bed with every muscle aching, headache, flu symptoms, swollen glands, more brain fog than usual and no appetite ( and no energy to eat).
Just coming out of such an episode after short synthacen test

 

This has been a sad yet hopeful thread for me, and reinforces the lack of general medical knowledge.

It' s clear from the posts that my daughter in fact had a relapse in Nov- Dec 2016 after having a diagnosis in September of that year from the paediatrician.

We had been given sheets on activity management and had very broad brush advice to start with small regular amounts of activity and build up. We found it difficult to find a baseline.
In retrospect advice should have been to do nothing until her body was ok doing nothing ( old fashioned convalescence) and then to expand things. This is so basic, yet so important.

Pressure from school, and from my daughter not wanting to fall further behind at school saw us engaged in home tutoring- a single subject but tackled with gusto and she soon caught up on 6 months work- pressured to do another subject but this did not work out ( she didn' t engage)
It' s now clear that this was all too much. The flu that she had in the Nov/ Dec was effectively a relapse, cognitive function became significantly impaired and she has never recovered to previous level.
Our paediatrician responded to a letter ( note my level of concern at what i thought were the effects of a cold virus) by advising that it was not uncommon for a cold virus to take longer to recover with CFS.....

PEM has since been acknowledged by paediatrician, but not in a way that suggested that it is a central feature of the condition - this may reflect the wide criteria for CFS diagnosis in children, and sadly this results in avoidable harm.

Luckily i found a parents' forum shortly afterwards, and PR and here therafter.
My daughter cannot do much without PEM kicking in, she has some things which in her ryes are worth " payback".
Sadly for a 16 year old these are mainly medical appointments.

By accurate description ( and the actual understanding and application), more appropriate diagnosis / advice may be possible.

 

Yes! This is a major PEM trigger for me also.

 

I am in the US and I didn't take it to mean "nausea". Never even crossed my mind. I took it to mean feeling "malaise" which is how I usually describe what "sick" feels like when I have PEM.