Myalgic Encephalomyelitis- Measuring Symptoms & Severity as well as PENE (also referred to as PEM)

While symptoms vary from patient to patient there are a few resources available to aid a proper understanding and to confirm a diagnosis, documents that can be used to highlight individual symptoms and disability. There are many general self-report tools available online but we feel that the ones we suggest below from De Paul University are the best available.

These are some of the useful questionnaires for measuring Myalgic Encephalomyelitis (ME) from the De Paul University. They include:

DePaul Symptom Questionnaire-2 (DSQ-2);

De Paul Pediatric Questionnaires for parent and child;

DePaul Post-Exertional Malaise Questionnaire.

Please see all available questionnaires via link here:

Measures – Leonard A. Jason (leonardjason.com)

More details about those useful De Paul Questionnaires & links

The DSQ-2 Symptom Questionnaire assesses key symptoms of ME such as post-exertional malaise, sleep, pain, neurological/cognitive impairments and autonomic, neuroendocrine and immune symptoms.

At each item, participants can rate the frequency and severity of the symptom on a scale from 0 to 4. You can put a score for how frequently you have each symptom and how severe it is.

The questionnaire is based on research so useful to print out to complete and show to your GP/Consultant/other.

As much as anything the questionnaire can teach your GP what ME is and you might realise things you think aren’t ME actually are!

(PDF) DePaul Symptom Questionnaire 2 (DSQ-2) (researchgate.net)

Paediatric Questionnaires

DePaul Symptom Questionnaire – Paediatric Screening Questionnaire (DSQ-PSQ): (PDF) DePaul Symptom Questionnaire - Pediatric Screening Questionnaire (DSQ-PSQ) (researchgate.net)

There is a parent and child form available so both adult and child can complete the questionnaires about the child with suspected ME or an ME diagnosis. Completed questionnaires can be used to inform medics re symptoms and severity and could also be used to track symptoms.

DSQ-PED Parent Form: (PDF) DePaul Symptom Questionnaire - Pediatric (Parent Report Form) (DSQ-PED Parent) (researchgate.net)

DSQ-PED Child Form: (PDF) DePaul Symptom Questionnaire - Pediatric (Child Report Form) (DSQ-PED Child) (researchgate.net)

The DPEMQ questionnaire:

Post exertional malaise (PEM) is a key symptom of Myalgic Encephalomyelitis (ME). The PEM questionnaire by De Paul is a questionnaire on the post exertional response in ME, i.e., PEM.

By answering the questions, you get an idea of how ‘activity’, anything you do physically, cognitively, emotionally, affects you and what your individual post exertional response is, i.e., what symptoms occur and increase.

Every person with ME is different. Post exertional response for a lot of people might not occur straight away and tends to be delayed 24 hours or 48 hours after activity.

The questionnaire includes key indicators that show within answering a short set of questions that your illness sounds like it is likely ME.

(PDF) DePaul Symptom Questionnaire - Post-Exertional Malaise short form (DSQ-PEM) (researchgate.net)

Thanks to Leonard Jason et al.

About Post Exertional Neuroimmune Exhaustion (PENE) in Myalgic Encephalomyelitis (ME)

Myalgic Encephalomyelitis (ME) & PENE have long been misunderstood derided & ignored. Believing this illness can be cured by attitude & effort is stigmatizing, harmful for individuals who blame themselves or get blamed for their suffering, & for the community of people deeply affected.

Image by JS

PENE is the cardinal feature of ME according to the International Consensus Criteria (2011) on ME.

PEM is often used to refer to PENE. PEM is a feature that occurs in other illnesses. 

PENE in ME is a distinct measurable feauture (see CPET test), while malaise as per PEM is subjective and not necessarily related to exhaustion or the nervous and immune systems.

PENE is particular to ME but we recognise and appreciate that PEM can be used when referring to the cardinal feature in ME.

There is a long list of atypical symptoms that occur when a person with ME suffers from PENE. Marked debilitating fatigue and weakness, sickness, cognitive dysfunction and symptom flare-up follows ANY physical or cognitive exertion requiring energy. Essentially what it means is that any exertion, physical, cognitive or even emotional stress creates a prolonged reaction in the body where a relapse or worsening of these ME symptoms occur and can last for days, weeks, months or longer. Indeed, many people who have pushed far too hard beyond their limits have become bedbound and carer dependent for years.

Worsening symptoms in ME as a result of PENE may include exhaustion, ‘flu-like’ symptoms, brain fog, cognitive dysfunction, word-finding problems, unrefreshing sleep, headaches, migraines, chronic pain, muscle pain and muscle fatigability, orthostatic intolerance, neurally mediated hypotension, or POTS, and much more. 

Another distinctive element of PENE is often described as a loss of stamina and/or functional capacity. (more on symptoms in the science section below)

NB: It is important to realise that at the severe end of the spectrum people with Severe ME don’t need to exert themselves for the phenomenon PENE to operate, it can simply be caused by reading a book or listening to a visitor. Even simple brain activity can lead to worsening of illness in ME.

The onset of PENE can be delayed 24-72 hours and depending on ME severity can last days, weeks, or even months

PENE Vs Fatigue

There is great importance in recognising Post Exertional Neuro-immune Exhaustion (PENE), also referred to as Post-Exertional Malaise (PEM), when it comes to diagnosing Myalgic Encephalomyelitis (ME). There is a significant difference between what a healthy person experiences after activity and what a person with ME experiences. The use of the same word ‘fatigue’ for both experiences often leads to endless misunderstandings and as a consequence can have a whole series of profound impacts on the person with ME and especially on those with Severe ME .

Let’s further explain about Post-Exertional Neuroimmune Exhaustion (PENE) as described in one of the best international guidelines for diagnosis and management we currently have …

As per the International Consensus Criteria (ICC) 2011, a patient will meet the criteria for (A) post exertional neuroimmune exhaustion, (B) at least one symptom from three neurological impairment categories, (C) at least one symptom from three immune/gastro‐intestinal/genitourinary impairment categories, and (D) at least one symptom from energy metabolism/transport impairments.

(A) Post exertional neuroimmune exhaustion (PENE) is the cardinal criterion for a diagnosis of ME according to the International Consensus Criteria (2011) on ME.

PENE means when you suffer from Myalgic Encephalomyelitis (ME) your symptoms get worse after you do things, and even after you do the smallest thing.

You may start to feel worse immediately afterwards or several days later. You may feel worse for a short time, or a long time, or indefinitely.

Some people experience worsened symptoms after light activity such as brushing teeth, walking to the bathroom, or after mental activity such as reading, chatting on the phone or watching tv. Some people can suffer PENE by just sitting up in bed or from the smallest movement like turning their head.

Essentially any action whether physical, cognitive, emotional, social, etc, drains available energy and if the ability to replace this energy is impaired this can lead to a worsening of all symptoms which can last for days, weeks or months – even causing permanent, non-recoverable systemic damage.

Assessment and Diagnosis of ME as per the ICC

As mentioned already, Post-Exertional Neuroimmune Exhaustion (PENE) is a compulsory criteria in the diagnosis of ME. This cardinal feature is a pathological inability to produce sufficient energy on demand with prominent symptoms primarily in the neuroimmune regions.

Meaning - My body does not produce enough energy.

Characteristics are:

1. Marked, rapid physical and/or cognitive fatigability in response to exertion, which may be minimal such as activities of daily living or simple mental tasks, can be debilitating and cause a relapse.

Meaning - After I do physical things, I feel worse or after I read or write or do other mental tasks, I feel worse. In Severe/Very Severe/Profound ME after I carried out the smallest movement while lying motionless in bed I feel profound and debilitating symptoms.

2. Post-exertional symptom exacerbation: e.g. acute flu-like symptoms, pain and worsening of other symptoms.

Meaning - After I do things, I feel like I have the worst flu, or feel pain, or feel worse in other ways. In Severe/Very Severe/Profound ME I feel extreme widespread pain, profound multiple sensitivities, shaking, trembling, paralysis and other extreme symptoms.

3. Post-exertional exhaustion may occur immediately after activity or be delayed by hours or days.

Meaning - I may not feel worse right away. I may start to feel worse in a few hours, or the next day, or the day after that. In Severe/Very Severe/Profound ME I can feel immediately worse.

4. Recovery period is prolonged, usually taking 24 hours or longer. A relapse can last days, weeks or longer.

Meaning - I can feel worse for a day, or for a few days, or for a few weeks, or longer.

5. Low threshold of physical and mental fatigability (lack of stamina) results in a substantial reduction in pre-illness activity level.

Meaning - I can no longer do the things I used to be able to do.

6. Cognitive fatigability in response to exertion.

Meaning- After I do things, I may feel worse physically or mentally. I may have problems with memory or concentration.

Information on PENE is based on the information provided in the International Consensus Criteria ICC 2011

Image by JS

Causes of PENE in Myalgic Encephalomyelitis (ME)

Physical over-exertion

Mental over-exertion

Emotional over-exertion

Sleep dysregulation

Unbalanced/poor diet and nutrition

Other medical issues

How to Prevent PENE in Myalgic Encephalomyelitis (ME)

There are a few ways to prevent PENE and to manage your ME symptoms. There is no single way of managing ME that works for everyone, and it takes time to figure out what works best for you. There are several management options. Early diagnosis, taking medication to control certain symptoms, and making lifestyle changes can all help. See more options below.

• Early Diagnosis and appropriate rest in the early stages of the illness.
• Pacing (activity management) & Resting
• Energy Envelope Technique - staying within your energy envelope
• Medical Treatments
• Management strategies e.g., Ensure good nutrition and appropriate sleep
• Using a Heart Rate Monitor
• Managing relapses and adrenaline surges in ME
• Learn your health patterns
• Practice techniques like meditation if you can
• Build your support community e.g., family, carers, doctors, specialists
• Maintain emotional health
• Avoid stress
• Treat other medical conditions
• Management of ME as per the International Consensus Primer, the ICP 2012

There are more details on each item in the above list of ways to prevent PENE and ways to manage your ME symptoms here.

NB:

Trial and Error. 

Management techniques mentioned above can help relieve some symptoms, but this is a matter of trial and error; the illness has an individual element - what helps one person might not work for the next. Your GP and/or specialist can help with a range of issues, including sleep disturbance, coping with pain and energy management.

Considerations for those with Severe and Very Severe ME. 

Due to the severity of illness in people with Severe and Very Severe ME, who would most likely be permanently confined to bed, care and treatment would be planned and catered to ensure that management of illness, dispensing of treatments and provision of meals and bathing is done in the most non-invasive way possible. As some Very Severe/Profound ME patients may be tube fed and administered meds intravenously there would be a very special care given to them.

More on Assessing PENE

1. The CPET Test

The distinctive element of PENE often described as a loss of stamina and/or functional capacity is referred to in the results of the 2-day cardiopulmonary exercise test (CPET) procedure.

The CPET is a procedure which assesses exercise capacity and recovery by performing two exercise tests 24 hours apart. The hypothesis is that ME patients display a characteristic deterioration in exercise capacity on the second test, a finding that has been reported by multiple research groups. This test is considered the gold standard for measuring physical capacity. 

A CPET is usually reproducible and normally has a test-retest difference of 7-12%. ME patients however show strikingly lower results on several measures at the second CPET compared to the first, despite meeting objective markers of maximal effort. The drop in functional capacity on the second CPET is usually not seen in other diseases.

According to Keller et al. (2014), “ME patients currently represent a unique class of ill patients who do not reproduce maximal CPET measures, unlike individuals with cardiovascular disease, lung disease, end-stage renal disease pulmonary arterial hypertension and cystic fibrosis".

A preliminary study from New Zealand suggests that patients with MS do not display the same decline on the second day of exercise testing, as do patients with ME.

“Once the disease was established the most characteristic symptom was extreme exhaustion, particularly after exercise. The exhaustion also occurred after emotional or mental strain.”

The CPET Test: "Cardiopulmonary Exercise Test Methodology for Assessing Exertion Intolerance in Myalgic Encephalomyelitis (ME) "

NB:

It is important to recognise that at the severe end of the spectrum people with Severe and Profound ME don’t need to exert themselves for the phenomenon PENE/PEM to operate, it can simply be caused by an attempt to read a book, watching tv or listening to a visitor. Even simple brain activity can lead to worsening of illness in ME. 

Questions raised about the clinical use of the 2-day CPET procedure in those with Severe ME by Snell et al (2013) suggested it might be unethical to use this method since many ME patients might suffer a serious relapse as a result of exercise performance. Other methods such as Heart Rate Monitoring or the De Paul DSQ-PEM Questionnaire are more suitable to those with more severe forms of ME.

2. De Paul DSQ-PEM Questionnaire

Assessments using tools such as self-reporting questionnaires, e.g. DSQ-PEM questionnaire by De Paul could be used where the CPET test may not be available to clinicians or where it is not practical for those with ME, especially people with severe ME. The questionnaire is a valuable tool for all severities to evidence PEM/PENE. Link here: DSQ-PEM Questionnaire

3. Simple Self Assessment

Ask yourself or the ME patient the following questions to simply assess PENE/PEM

1. What kind of exertion triggers your PENE/PEM? 

2. Does PENE/PEM happen

   1. minutes after exertion

   2. hours after exertion

   3. a day or more after exertion

   4. not at all

3. Please describe what happens to you when PENE/PEM occurs 

4. How long does it take you to recover from PENE/PEM? 

   1. at least a day

   2. several days

   3. at least a week

   4. several weeks

   5. a month or more

5. What do you do to recover from PENE/PEM? 

6. What do you do to prevent PENE/PEM from occurring?

4. Using a Heart Rate Monitor

See section about heart rate monitor usage in previous post via link above and again here: ME Advocates Ireland (MEAI): Managing & Treating Myalgic Encephalomyelitis (ME)

The Science about PENE/PEM in Myalgic Encephalomyelitis (ME)

Symptoms in ME potentially made worse due to physical or cognitive exertion

The Jason et al 2019 study entitled, ‘Assessment of Post-Exertional Malaise (PEM) in Patients with Myalgic Encephalomyelitis (ME)’ refers to a list of symptoms in ME which are potentially made worse due to physical or cognitive exertion. See the full study based on feedback from 1534 patients who responded to questions about PEM here.

Table 4. from the study by Leonard Jason et al shows a list of symptoms caused or made worse by exertion, see below.

Items	% (n) “Yes”	% (n) at “2” Threshold	Mean (SD)
1. Reduced stamina and/or functional capacity	99.4 (1525)	98.0 (1504)	90.60 (17.16)
2. Physical fatigue	98.9 (1517)	98.3 (1508)	87.53 (18.26)
3. Cognitive exhaustion	97.4 (1494)	92.0 (1412)	77.64 (24.87)
4. Problems thinking	97.4 (1494)	92.6 (1420)	78.47 (24.87)
5. Unrefreshing sleep	95.0 (1457)	91.1 (1398)	80.57 (27.65)
6. Muscle pain	87.9 (1349)	81.5 (1250)	69.41 (33.95)
7. Insomnia	87.3 (1339)	75.1 (1152)	62.40 (34.30)
8. Muscle weakness/instability	87.3 (1339)	77.2 (1185)	64.03 (33.86)
9. Temperature dysregulation	86.9 (1333)	75.2 (1153)	63.76 (34.75)
10. Flu-like symptoms	86.6 (1329)	74.4 (1142)	59.52 (33.43)
11. Aches all over your body	85.6 (1313)	79.5 (1219)	68.68 (35.58)
12. Physically fatigued while mentally wired	82.1 (1259)	72.8 (1116)	59.00 (35.65)
13. Dizziness	80.7 (1238)	56.0 (859)	46.28 (33.19)
14. Gastro-intestinal problems	78.6 (1206)	59.3 (910)	49.90 (36.02)
15. Headaches	78.0 (1197)	56.5 (866)	46.48 (34.52)
16. Ataxia	77.6 (1191)	57.8 (886)	47.62 (35.18)
17. Increased heart rate/heart palpitations	77.4 (118)	64.9 (996)	52.28 (36.51)
18. Weak or stiff neck	74.6 (1144)	61.0 (936)	51.35 (38.20)
19. Joint pain	73.0 (1120)	59.5 (912)	49.17 (37.86)
20. Problems with speech	72.4 (1110)	50.0 (767)	40.22 (33.14)
21. Sore throats	70.9 (1087)	47.2 (724)	38.92 (33.55)
22. Muscle twitching	68.1 (1045)	40.9 (627)	35.12 (32.38)
23. Night sweats and chills	67.7 (1038)	46.9 (720)	38.48 (34.69)
24. Sore eyes	67.0 (1028)	49.0 (752)	39.91 (35.70)
25. Nerve pain	63.3 (971)	48.8 (748)	40.65 (38.16)
26. Sore lymph nodes	62.9 (965)	44.0 (675)	36.36 (35.28)
27. Nausea	62.2 (954)	38.1 (584)	31.89 (32.13)
28. Tinnitus	60.3 (925)	39.8 (611)	37.42 (38.96)
29. Trouble breathing	57.8 (887)	40.9 (628)	33.97 (35.67)
30. Neurological symptoms	57.0 (875)	42.8 (656)	34.60 (36.14)
31. Excessive sleep	54.4 (835)	44.5 (682)	36.23 (38.58)
32. Loss of appetite	49.0 (752)	30.9 (474)	25.41 (31.62)
33. Migraines	46.2 (708)	24.6 (378)	21.92 (29.27)
34. Cardiac pain and/or arrhythmia	41.2 (632)	24.8 (381)	21.12 (30.30)
35. Brain twangs	29.9 (459)	17.7 (272)	15.00 (26.82)
36. Severe burning sensation all over skin	29.7 (456)	18.3 (280)	15.96 (28.87)
37. Paralysis/inability to move	29.4 (451)	9.4 (144)	11.49 (21.91)
38. Premenstrual symptoms	21.1 (323)	16.4 (251)	13.56 (29.25)
39. Decreased heart rate	15.1 (231)	7.4 (114)	6.88 (19.09)

Image by JS

More on the Science about PENE

Scientific Papers behind PENE compiled by Dr Mark Gutheridge

A study by the Workwell Foundation et al shows that ME patients have metabolic defects that cannot be explained by exercise phobias, deconditioning or 'illness beliefs'. People with ME have reduced oxygen consumption during exercise tests.
Properties of measurements obtained during cardiopulmonary exercise testing in individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - IOS Press

People with ME have an impaired ability to increase their oxygen consumption during exercise. This is entirely different to every other disease we know including cardiovascular disease, lung disease, end-stage renal disease, hypertension & cystic fibrosis.

Inability of myalgic encephalomyelitis/chronic fatigue syndrome patients to reproduce VO2peak indicates functional impairment | Journal of Translational Medicine | Full Text (biomedcentral.com)

People with ME also show impaired oxygen consumption and reduced anaerobic threshold compared to Multiple Sclerosis.

Physiological measures in participants with chronic fatigue syndrome, multiple sclerosis and healthy controls following repeated exercise: a pilot study - Hodges - 2018 - Clinical Physiology and Functional Imaging - Wiley Online Library

Exercise testing provides an explanation for why people with ME can crash even after modest exertion. The reduced aerobic capacity of people with ME results in a switch to anaerobic metabolism that likely impacts their ability to do simple daily activities.

Frontiers | Chronotropic Intolerance: An Overlooked Determinant of Symptoms and Activity Limitation in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome? (frontiersin.org)

ME patients can 'crash' if they over-exert resulting in a post-exertional malaise (PEM). Triggering PEM reduces the threshold at which anaerobic metabolism accelerates which impairs the ability of patients to do non-strenuous tasks.

Inability of myalgic encephalomyelitis/chronic fatigue syndrome patients to reproduce VO2peak indicates functional impairment | Journal of Translational Medicine | Full Text (biomedcentral.com)

And exercise that triggers PEM in ME patients leads to a sustained immune inflammatory response that is distinct from that in sedentary or deconditioned people.

Deconstructing post-exertional malaise in myalgic encephalomyelitis/ chronic fatigue syndrome: A patient-centered, cross-sectional survey | PLOS ONE

People use aerobic metabolism for the majority of daily activities such as walking and seated tasks, but a reduced aerobic capacity of ME patients likely forces a switch to less efficient anaerobic metabolism leading to premature fatigue and PEM.

Frontiers | Cardiopulmonary Exercise Test Methodology for Assessing Exertion Intolerance in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (frontiersin.org)

Exercise studies also show that the increased reliance on anaerobic metabolism in ME patients results in increased metabolites such as lactic acid which likely leads to an inability to maintain work and a reduction in activity.

Discriminative Validity of Metabolic and Workload Measurements for Identifying People With Chronic Fatigue Syndrome | Physical Therapy | Oxford Academic (oup.com)

Physical therapists should be aware that post-exertional malaise (PEM) in people with ME is due to objectively measurable deficits in metabolism. So yes, exercise is beneficial for nearly every illness.....but the science shows that ME is the exception.

Discriminative Validity of Metabolic and Workload Measurements for Identifying People With Chronic Fatigue Syndrome | Physical Therapy | Oxford Academic (oup.com)

This Frontiers review by Workwell discusses how cardiopulmonary exercise testing (CPET)can be used to help diagnose & research ME.
Frontiers | Cardiopulmonary Exercise Test Methodology for Assessing Exertion Intolerance in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (frontiersin.org)

Included in the study is Table 1. which provides a helpful list of definitions for patients and doctors to investigate ME.

The Problems that arise when the Science is Ignored

Myalgic Encephalomyelitis (ME), & PENE in ME has long been misunderstood, derided & ignored. Believing this illness can be cured by attitude & effort is stigmatizing, harmful for individuals who blame themselves or get blamed for their suffering, & for the community of people deeply affected.

PENE is not ......

‘exaggerating’ ‘imagining it’ ‘aging’ ‘depression’ ‘menopause’ ‘laziness’ ‘being overweight’ ‘normal, everyone gets tired’ ‘anxiety’ ‘work refusal’ ‘psychiatric’ ‘exercise intolerance’ ‘a woman’s illness’ ‘extreme tiredness’

‘hysteria’ ‘mental illness’ ‘MUS’ ‘chronic fatigue’ ‘deconditioning’ ‘perfectionism’ ‘conversion disorder’ ‘psychosomatic’ ‘middle age issue’ ‘Munchausen syndrome by proxy’ ‘school avoidance’ ‘emotionally distressed’ ‘anti-science’ ‘anti-medics’ ‘activists’ ‘hypochondriac’

More Educational Pieces about PENE in Myalgic Encephalomyelitis (ME)

‘Dialogues For a Neglected Illness’

The short films about PENE, referred to as PEM, ‘A Brief Guide to PEM’, ‘Understanding PEM’ and 'Patients' Accounts of Symptoms - Post Exertional Malaise' from ‘Dialogues for a neglected illness’ (Dialogues for ME) raise awareness of the effects of activity/exertion within ME, in particular within the severe category, how some may be affected by pottering for an hour whereas for others the slightest exertion such as thinking of trying to read, will trigger PENE.

The films show how exertion does not necessarily need to be what would normally be described as exertion, yet can still have a deteriorative impact leading to a worsening of symptoms.

The films portray reality where at the severe end of the spectrum people with Severe ME don’t need to exert themselves for the phenomenon PENE to operate, it can simply be caused by reading a book or listening to a visitor, even simple brain activity can lead to worsening of illness in ME.

A common characteristic of PENE described is that it can be elicited by multiple types of triggers.

Films available here: Post-Exertional Malaise - Dialogues (dialogues-mecfs.co.uk)

“ME patients describe post–exertional malaise as all-encompassing with symptoms affecting every part of the body, difficult to predict or manage, and requiring complete bedrest to fully or partially recover.”

Image by JS

'What a failure of our medical “system” that people go years with PEM and no one puts the pieces together for them. I can’t even conceive of the othering my patients have to live with daily but I’m reminded every time a patient cries when we simply discuss the science of PEM.'

~ Todd Davenport, Professor & Vice Chair, Department of Physical Therapy, University of the Pacific Stockton, California, US

Compiled by MD on behalf of MEAI

Nov 2022