Myalgic Encephalomyelitis (ME) & the cardinal feature Post Exertional Neuro-Immune Exhaustion 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|
Post Exertional Neuroimmune Exhaustion - PENE, is the cardinal feature of ME according to the International Consensus Criteria (2011) on ME.
Post Exertional Neuroimmune Exhaustion - PENE is the cardinal feature of ME according to the International Consensus Criteria and Primer on ME.
Post Exertional Neuroimmune Exhaustion - PENE is a feature that is synonymous with ME. PENE in ME is a distinct measurable feature related to exhaustion and the nervous and immune systems.
Post Exertional Neuroimmune Exhaustion - PENE is particular to ME, however we recognise and appreciate that PEM can be used when referring to this cardinal feature in ME, though PEM is common in other illnesses too.
There is a long list of atypical symptoms that occur when a person with ME suffers from Post Exertional Neuro-Immune Exhaustion - PENE; marked debilitating illness and weakness, cognitive dysfunction, symptom flare-up and possible paralysis as seen in severe ME, can follow ANY physical or cognitive exertion requiring energy, no matter how small or insignificant the exertion.
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 Post Exertional Neuroimmune Exhaustion -PENE may include exhaustion, extreme chronic pain, paralysis, brain fog, cognitive dysfunction, unrefreshing sleep, headaches, migraines, muscle pain and muscle fatigability, orthostatic intolerance, neurally mediated hypotension, or POTS, inability to eat, swallow or digest food, and much more.
Another distinctive element of Post Exertional Neuroimmune Exhaustion - PENE is often described as a loss of stamina and/or functional capacity. (more on symptoms further below)
Note: 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, there can be a critical response to the slightest movement by the patient or by the movement of a visitor to the patient's bedroom. Even simple brain activity can lead to worsening of illness in ME, e.g., hearing noise from outside the bedroom.
The onset of Post Exertional Neuroimmune Exhaustion - PENE can occur immediately, hours later or delayed up to 24-72 hours and depending on ME severity can last days, weeks, or even months.
We explored the differences between patients in an informal survey during May awareness month 2023. The survey feedback shows differences among ME patients in the response time for PENE to occur and to last, and the differences an individual may have, showing that most with ME don't have a set pattern re PENE occurring or with regards to how long symptoms associated with PENE will last. See the response to survey question about these features of PENE below:
Does PENE (also referred to as PEM) happen straight away or minutes after exertion or hours after exertion or a day or more after exertion?
Post Exertional Neuroimmune Exhaustion - PENE Vs Fatigue
There is great importance in recognising Post Exertional Neuro-immune Exhaustion (PENE), 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 International Consensus Criteria )(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.
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
Causes of Post Exertional Neuro-Immune Exhaustion (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 Post Exertional Neuro-Immune Exhaustion (PENE) in Myalgic Encephalomyelitis (ME)
There are a few ways to prevent PENE and to manage 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 ME symptoms here
Note: 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.
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.
Survey Feedback - The Post Exertional Neuro-immune Exhaustion (PENE) feature in ME
We held an informal survey during May awareness month 2023 to find out more about patients' individual experiences with regards to Post Exertional Neuro-Immune Exhaustion - PENE.
Here are the questions we asked:
Q1 What words do you use to describe PENE (also referred to as PEM), the response you have after exertion whether physical or mental exertion or in response to a hyper sensitivity stimulus or action, e.g. 'relapse' ?
Q2 What kind of exertion triggers your PENE/PEM?
Q3 Does PENE (also referred to as PEM) happen... straight away or minutes after exertion or hours after exertion or a day or more after exertion?
Q4 How do you avoid PENE (or PEM), the post exertion response/crisis?
Q5 What can you do to recover from PENE, the post exertion response/crisis?
Q6 If you could provide one piece of advice to a person newly diagnosed with ME or to someone who suspects ME what would it be?
Please see the feedback from an informal survey on Post Exertional Neuro-Immune Exhaustion - PENE which we held during ME awareness month 2023 here
The Science Behind Post Exertional Neuro-Immune Exhaustion (PENE) 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)|
More on the Science about PENE
Scientific Papers behind PENE compiled by Dr Mark Gutheridge
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)
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
Deconstructing post-exertional malaise in myalgic encephalomyelitis/ chronic fatigue syndrome: A patient-centered, cross-sectional survey | PLOS ONE
Discriminative Validity of Metabolic and Workload Measurements for Identifying People With Chronic Fatigue Syndrome | Physical Therapy | Oxford Academic (oup.com)
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.”
'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