Dissecting the nature of post-exertional malaise (PEM)

Posted on: 27th November, 2020

Authors: Lucinda Bateman, Suzanne D. Vernon, Megan Hartle

DOI: 10.1080/21641846.2021.1905415.

Introduction

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disease with significant unmet medical needs that affects as many as 2.5 million people in the U.S. and causes enormous burden for patients, their caregivers, the healthcare system, and society. The disease is characterized by impaired function accompanied by severe fatigue, unrefreshing sleep, cognitive impairment, and orthostatic intolerance, all of which are worsened by physical and cognitive exertion causing post-exertional malaise (PEM) . ME/CFS is generally considered to be a post-viral or post-infection syndrome with immune, metabolic, and neurologic sequelae . Because fatigue is a common symptom of many different medical and psychiatric conditions, the rate of misdiagnosis of ME/CFS can be as high as 40–50% of cases . Furthermore, numerous case definitions and the lack of objective diagnostic biomarkers result in many people not getting a diagnosis . At least one-quarter of ME/CFS patients are house- or bedbound at some point in their lives. The economic impact of ME/CFS is $17 to $24 billion annually for direct costs and $9.1 billion from lost household and labor force productivity.

Post-exertional malaise (PEM) is the cardinal and distinguishing feature of ME/CFS. As the phrase suggests, PEM is an increase in severity of symptoms (e.g. fatigue, weakness, orthostatic intolerance) and signs (e.g. heart rate variation, temperature dysregulation) that occurs following physical and cognitive exertion. Patients report that PEM can be triggered by the most mundane of daily activities including sitting upright at the dining table, standing to make a salad, taking a shower, driving a car, grocery shopping and cleaning the house. Cognitive exertion that triggers PEM can occur by listening to a lecture, socializing, having a conversation or reading. Upright posture (defined as feet on the floor) that occurs during physical and cognitive activities (e.g. walking, sitting at a desk) may be sufficient exertion to trigger PEM. Our clinical observations of hundreds of ME/CFS patients indicate that less time in an upright posture with feet on the floor over a 24-h period is associated with severe illness symptoms and disability. Patients with <5 h of upright activity (with feet on the floor) were more likely to be home or bedbound and unemployed compared to patients with ≥5 h of upright activity.

We were interested in understanding ME/CFS patients’ perspective of PEM in order to identify point-of-care methods to assess PEM for diagnosis. ME/CFS patients participating in an ongoing longitudinal study responded to an online PEM questionnaire during the first year. The PEM questionnaire used open-ended text responses to capture patients’ personal stories about PEM triggers, experiences, recovery, and prevention. Our objective was to review the responses, recode them to categorical topics and determine if there were differences in PEM by duration of illness.

Methods

A PEM questionnaire administered to 150 ME/CFS patients. It included open-ended questions about triggers, experiences, recovery, and prevention. Responses were re-coded into concise, representative topics. Chi-Square tests of independence were then used to test for differences and relationships between duration of ME/CFS illness (<4 years and >10 years), PEM onset and duration, and gender with PEM trigger, experience, recovery, and prevention.

Results

Physical exertion was the most common trigger of PEM. The onset of PEM occurred within minutes after physical exertion compared to within hours after cognitive exertion (<0.05). ME/CFS patients sick for <4 years reported stress as a trigger significantly more often than those sick for >10 years (<0.001). ME/CFS patients sick for <4 years experienced more orthostatic symptoms during PEM than those sick for >10 years. ME/CFS patients sick for >10 years reported using medications to recover from PEM significantly more that those sick for <4 years (<0.01). Pacing and avoiding specific triggers were common approaches to prevent PEM.

Conclusions

There are differences in PEM triggers, experiences and recovery based on duration of illness. Asking about PEM is important for diagnosis and to understand how to manage PEM. Given that PEM occurs more quickly after physical versus cognitive exertion, these results should instigate research on the relationship of upright posture, hypoperfusion and PEM.

The published journal article can be read on the https://www.tandfonline.com/doi/full/10.1080/21641846.2021.1905415?scroll=top&needAccess=true#abstract