Post Exertional Malaise (PEM) in ME/CFS and Long Covid

1.   What is Post Exertional Malaise?

Post exertional malaise  or PEM, is a unique type of fatigue experienced in ME/CFS and also found in Long Covid. It is a defining feature of ME/CFS and is used in the diagnosis of this condition. It is also sometimes called ”post-exertional neuroimmune exhaustion ” (PENE).

The term was first used 1950s, Dr Melvin Ramsey, the infectious disease physician who created the term myalgic encephalomyelitis and considered PEM “as the sheet anchor of diagnosis”. He described PEM as:

Another researcher more recently described this symptom as follows:

Unusually, the onset of this type of fatigue can be delayed for 24-72 hours and, depending on ME/CFS severity, can last days, weeks, or even months.

2.   Five defining features of PEM

The specific characteristics of PEM have been identified by research which used data from patient experience and biomedical studies using exercise tests. These are shown in the diagram 1 below.

Diagram 1. The defining features of Post-Exertional Malaise (PEM) (Cotler 2018)

3.   What triggers PEM?

Focus groups have outlined that a broad set of non-strenuous daily activities that may trigger PEM, such as:

• household chores

• social activities

• physical exercise

• cognitive activities, and

• emotional moments

  
  

Even basic activities of daily living such as toileting, bathing, dressing, communicating, and reading can trigger relapses. Triggers can be cognitive, physical or emotional.

Diagram 2: Examples of Cognitive, physical and emotional factors that can trigger PEM (Stussman, 2020)

4.   Symptoms of Post Exertional Malaise

The range of PEM symptoms can include:

• Flu-like symptoms including headaches, sore throat, muscle aches and weakness, chills, and swollen glands

• Nausea and loss of appetite

• A heavy feeling in the limbs or body

• Increased sensitivity to sound, light, or smell

• Loss of stamina and an increase in fatigue

• Dizziness

• Feeling too cold or too hot

• Ringing in the ears

• Muscle weakness, trembling, or instability

• Heart palpitations

• Burning sensations on the skin

• "Brain fog" or difficulty concentrating, focusing, and thinking

• Speech and word-finding problems

• Sleep disruptions including insomnia, nightmares, or sleeping too much

5.   The experience of PEM

What does PEM feel like when you experience it?

People with ME/CFS say post-exertional malaise feels like a "crash" or a "collapse." “flare-up,” “debility”, ”wiped out”, “exhaustion” or “set-back”

Source: ME-Pedia https://me-pedia.org/wiki/Post-exertional_malaise#cite_note-IOM2015-40

In 2018 Lily Chu and colleagues undertook a detailed study of PEM in  ME/CFS. One hundred and fifty people with a CFS diagnosis (Fukuda criteria) completed a survey about 11 symptoms experienced after two types of trigger. Key findings were as follows:

• 90% (129) experienced PEM following physical and cognitive exertion and most, after emotional distress as well

• Fatigue was the most common symptom that worsened, but cognitive difficulties, sleep disturbances, headaches, muscle pain, and flu-like feelings were experienced by 30%

• 60% experienced at least one inflammatory/immune-related symptom

• Other symptoms included gastrointestinal, orthostatic, mood-related, and neurologic symptoms

Fatigue in PEM

The word fatigue seems inadequate to describe the feelings of exhaustion felt by people suffering from PEM. One study, (Keech, 2015) analysed the words used by people who experienced PEM and identified 5 themes as shown below:

6.   Timing of symptoms of PEM

PEM often has a delayed onset, with symptoms arising hours or even days after a trigger. PEM is therefore different from fatigue suffered in other fatiguing illnesses. The study by Chu and colleagues (2018) found that 37% of 150 patients did not have symptoms until a day or more after a trigger with 11% reporting a consistent post-trigger delay of at least 24 hours before onset.

 Diagram showing time lapse after trigger before symptoms of PEM in study by Chu, 2018

One participant made the following comment on their experience of PEM:

7.   How long does PEM last?

The duration of PEM symptoms is very variable. The study by Chu found:

• 
  

• 84% endure PEM for 24 hours or more

• In 35% of people PEM lasted a few hours

• In 38% of people PEM duration was 3-7 days

• 25% of people said PEM could last as long as weeks and 14% said it could last even months

• A few commented that their time patterns varied so much it was difficult even to put down a range

• Variations frequently depended on the type and intensity of activity

Diagram showing duration of PEM symptoms in study by Chu, 2018

These findings on delayed onset  and duration of PEM have also been shown by studies undertaken by the Workwell Foundation, (Van Ness, 2010 and Davenport, 2011). They used cardiopulmonary exercise tests to compare experience of people with ME/CFS with healthy controls. They found that compared to healthy controls, the ME/CFS subjects:

• Experienced some symptoms the healthy subjects did not experience at all e.g light-headedness, sore throat/ swollen glands, cognitive dysfunction

• Were significantly more likely to experience other symptoms e.g. pain and sleep disturbance

• The time course of symptoms also differed substantially:

• Most control subjects experienced the peak of their symptoms on the day of the test and 87%-95% of them had recovered fully 24 hours later

• Some ME/CFS subjects’ symptoms peaked 24 or 48 hours after the test with 45%-60% of ME/CFS subjects still feeling the effects after 5 days.

8.   PEM in Long Covid

PEM has been identified as a common symptom in Long Covid. The WHO states:

“Post-exertional malaise (PEM) is fatigue and worsening of symptoms following even minor physical or mental exertion. It is commonly reported by people with post COVID-19 condition, and can impair their ability to exercise, work or go about daily activities”

One study (Jason and Dorri, 2023) assessed 465 patients with Long Covid in a study which included the DSQ-PEM tool, found that 58% of patients met the CCC criteria for ME/CFS.

Another study (Davis, 2021) looked at the key characteristics of Long Covid  and found  that 89% of patients reported experiencing either physical or mental PEM. PEM was triggered at various time points after exertion, and, for most, lasted a few days.

Diagram showing key characteristics of Long Covid, showing frequency of PEM (Davis,2021)

References

Chu L, Valencia IJ, Garvert DW, Montoya JG. Deconstructing post-exertional malaise in myalgic encephalomyelitis/ chronic fatigue syndrome: A patient-centered, cross-sectional survey. PLoS One. 2018 Jun 1;13(6):e0197811. doi: 10.1371/journal.pone.0197811. PMID: 29856774; PMCID: PMC5983853

Cotler, Joseph; Holtzman, Carly; Dudun, Catherine; Jason, Leonard A. (September 11, 2018). "A Brief Questionnaire to Assess Post-Exertional Malaise". Diagnostics (Basel, Switzerland). 8 (3). doi:10.3390/diagnostics8030066. ISSN 2075-4418. PMID 30208578

Stussman B., et al. (2020). Characterization of post-exertional malaise in patients with myalgic encephalomyelitis/chronic fatigue syndrome. Front. Neurol. 11, 1025. 10.3389/fneur.2020.01025 

Keech, Andrew et al, 2015. "Capturing the post-exertional exacerbation of fatigue following physical and cognitive challenge in patients with chronic fatigue syndrome". Journal of Psychosomatic Research. 79 (6): 537–549. doi:10.1016/j.jpsychores.2015.08.008. ISSN 1879-1360

Chu L, Valencia IJ, Garvert DW, Montoya JG. Deconstructing post-exertional malaise in myalgic encephalomyelitis/ chronic fatigue syndrome: A patient-centered, cross-sectional survey. PLoS One. 2018 Jun 1;13(6):e0197811. doi: 10.1371/journal.pone.0197811. PMID: 29856774; PMCID: PMC5983853.

Van Ness JM, Stevens SR, Bateman L, Stiles TR, Snell CR. Post exertional malaise in women with chronic fatigue syndrome. J Women’s Health. 2010; 19:239–44

Davenport TE, Stevens SR, Baroni K, Van Ness JM, Snell CR. Diagnostic accuracy of symptoms characterising chronic fatigue syndrome. Disabil Rehabil. 2011; 33:1768–75. doi: 10.3109/09638288.2010.546936

Jason, Leonard A., and Joseph A. Dorri. 2023. "ME/CFS and Post-Exertional Malaise among Patients with Long COVID" Neurology International 15, no. 1: 1-11. https://doi.org/10.3390/neurolint15010001

Davis HE, Assaf GS, McCorkell L, Wei H, Low RJ, Re'em Y, Redfield S, Austin JP, Akrami A. Characterizing long COVID in an international cohort: 7 months of symptoms and their impact. EClinicalMedicine. 2021 Aug;38:101019. doi: 10.1016/j.eclinm.2021.101019. Epub 2021 Jul 15. PMID: 34308300; PMCID: PMC8280690.