Among patients with myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS), post-exertional malaise (PEM) has long been considered a hallmark symptom [1
]. However, in a field which includes more than twenty case definitions for ME and CFS, there has not been agreement regarding defining PEM [2
]. For example, discrepancies occur with two of the most frequently used ME and CFS case definitions, the Fukuda [3
] and Canadian Consensus Criteria (CCC; [4
]). The Fukuda et al. criteria do not define the term beyond requiring that it last for more than 24 h nor does it make PEM a requirement for diagnosis. In contrast, the CCC case definition requires the presence of PEM for diagnosis and goes further to describe the symptomatic experience as similar to flu-like distress, with a potential delayed onset [4
Several activity and self-report measurements that assess the extent of activity and how such activity might result in exacerbation of symptoms have been proposed to measure PEM. These include actigraphy, exercise challenges, time logs, and self-reports [5
]. For example, following an exercise task, Mateo et al. [6
] reported a broad spectrum of PEM-related symptoms including fatigue, muscle/joint pain, cognitive dysfunction, decrease in function, headaches, sleep disturbances, pain, weakness, cardiopulmonary symptoms, lightheadedness, and flu-like symptoms. Others have found using self-report measures that PEM comprises two distinct constructs: muscle-specific fatigue and generalized fatigue [7
Factors which elicit PEM include physical and cognitive exertion. For some patients, even basic activities of daily living such as toileting, bathing, dressing, communicating, and reading can trigger PEM. However, many patients feel that potential triggers should extend beyond these types of stressors and include infections [8
], exposure to chemicals or certain foods [9
], or exposure to certain metals [10
]. Additionally, many efforts to assess PEM have not included a characteristic delay in the onset of PEM. Chu et al. [11
] maintain that this delay is rarely found in other fatiguing illnesses. Another issue that has often not been included in the assessment of PEM is that many patients with ME and CFS take considerably longer to recover from a trigger [12
], reporting a substantial increase in symptoms immediately after an exercise test, the next day, and even a week later [13
In an effort to address these PEM-related discrepancies, the National Institutes of Health/Center for Disease Control and Prevention (NIH/CDC) Common Data Element (CDE) committee’s PEM working group attempted to define PEM [14
] as “an abnormal response to minimal amounts of physical or cognitive exertion that is characterized by: (1) Exacerbation of some or all of an individual study participant’s ME/CFS symptoms. (2) Loss of stamina and/or functional capacity. (3) An onset that can be immediate or delayed after the exertional stimulus by hours, days, or even longer. (4) A prolonged, unpredictable recovery period that may last days, weeks, or even months. (5) Severity and duration of symptoms that is often out-of-proportion to the type, intensity, frequency, and/or duration of the exertion.” Yet, there was no set of items with anchor points associated with these 5 descriptors of PEM offered by the NIH/CDC CDE PEM working group. While the general guidance of the committee was helpful, these types of general descriptions need to be operationalized if investigators are to reliably use them to assess PEM. The NIH/CDC CDE’s PEM working group also recommended the use of 5 items from the DePaul Symptom Questionnaire (DSQ, [12
]) to measure PEM (e.g., physically drained or sick after mild activity). However, the DSQ was not developed as a comprehensive measure of PEM but rather as a measure of ME and CFS symptomatology as a whole. Following the release of the NIH/CDC CDE’s PEM recommendations, patients were extremely concerned with the recommendations that had been made [15
This latest NIH/CDC CDE’s recommendations regarding the measurement of PEM needs to be understood in the context of a long history where patients have felt left out of key policy decisions imposed on them, including how to name, define, and treat ME and CFS. As one example, when the Institute of Medicine (IOM; [16
]) recommended a new name and case definition, this created considerable controversy, as many feel that both were decisions imposed on the patient community, without first seeking their input and approval.
The recent recommendations made by this NIH/CDC CDE’s PEM working group, and the vociferous reactions to it by the patient community, provided an opportunity to engage in community-based participatory research, which equitably involves all partners in the research process [17
]. Given the importance of PEM, and the patient community’s resentment regarding once again not being active participants in the development of this latest PEM recommendation, the current authors decided to try to develop a comprehensive measure with active collaboration of the patient community. We hypothesized that a valid PEM instrument could be created with the help of the patient community.
The international online convenience sample included 1,534 adults identifying as having ME and/or CFS who completed the questionnaire (347 additional respondents had incomplete surveys and were not included in this analysis). Respondents were from over 35 countries. As indicated in Table 1
, 41.1% of participants reported currently living in the United States. The sample consisted of mostly females (84.6%). The majority of participants were white/Caucasian (97.5%), and 2% identified as being of Latino or Hispanic origin. Just over half of the participants were married or living with a partner (56.6%), 39.3% had a standard college degree, and 45.7% were receiving disability payments.
indicates that 50.7% of participants had a diagnosis of CFS, 22.0% had a diagnosis of ME, and 27.2% had a diagnosis of both ME and CFS. For our entire sample, 94.4% reported being diagnosed by a medical doctor.
Descriptive statistics of PEM onset are reported in Table 2
. Over half of participants had experienced onset of symptom exacerbation immediately after exertion (72.3%), while 91.4% had experienced delayed onset after exertion. To determine the length of the delay between exertion and the onset of PEM, participants selected periods for when the onset of PEM might occur when onset is delayed. A delay of between 1–2 days after exertion was experienced by 53.1% of the participants.
describes PEM triggers, with 78.2% endorsing “basic activities of daily living”, 64.5% endorsing “positional changes”, and 93.2% endorsing “emotional stress (good or bad)”. Additionally, 84.9% said there were some instances in which the specific precipitants could not be identified. The highest endorsed non-exertion triggers reported by participants were as follows: emotional events (88.3%), noise (85.5%), and sensory overload (83.6%).
reports the proportion of participants who endorsed the worsening of symptoms due to physical or cognitive exertion. The most commonly endorsed symptoms were as follows: reduced stamina and/or functional capacity (99.4%), physical fatigue (98.9%), cognitive exhaustion (97.4%), problems thinking (97.4%), unrefreshing sleep (95.0%), muscle pain (87.9%), insomnia (87.3%), muscle weakness/instability (87.3%), temperature dysregulation (86.9%), and flu-like symptoms (86.6%). The symptoms endorsed by less than half of the sample included the following: loss of appetite (49.0%), migraines (46.2%), cardiac pain and/or arrhythmia (41.2%), brain twangs (29.9%), burning sensation all over your skin (29.7%), paralysis/inability to move (29.4%), pre-menstrual symptoms (21.1%), and decreased heart rate (15.1%).
In order to gauge participant’s general experiences of PEM, participants were asked if they experienced any of the common phrases used to describe PEM (listed in Table 5
) after exertion. All of the phrases were endorsed by over 90% of the sample.
The findings reported in Table 6
indicate that over half the participants (58.0%) said PEM lasts on average 3–6 days, with 1–2 days (38.9%), 1 week–1 month (46.7%), and 1–6 months (30.3%) also being frequently reported. Additionally, 67.1% of the sample had experienced a “crash” that never resolved. Over half of the sample (57.2%) said they had experienced an adrenaline surge during or after going beyond their energy limits, and the most commonly reported length of time was “a few hours” (35.8%). Further information about the natural history of participants’ ME/CFS illness are also provided in Table 6
. The majority of subjects have been sick for over 10 years, with 97.1% reporting their illness being present for more than 50% of the time. Additionally, nearly half of participants described the course of their illness as fluctuating, experiencing good periods and bad periods. Lastly, nearly half of participants classified their status as being able to do light house work, but not being able to work part-time.
also contains information on how participants were currently managing their PEM symptoms. Only 6% of patients with ME or CFS felt that pacing completely allowed them to avoid PEM, while the majority reported pacing only being effective some of the time and only at a moderate/mild level. Participants also identified the pacing method they used (e.g., 87.1% indicated it was based on their bodies’ reactions whereas 10.7% indicated it was with a heart rate monitor, and 17.3% indicated both).
Patients were also asked about tests to assess their cardiovascular health difficulties and orthostatic intolerance, which are common symptoms of ME and CFS and are often made worse after exertion. Almost a quarter (24.5%) indicated they had undergone a cardiopulmonary test and 29.7% indicated they had taken part in a stand lean/tilt table test. Of those patients, 9.3% had normal cardiopulmonary results, whereas 14.9% had abnormal results. Only 4.8% of the sample had completed an exercise test on back-to-back days.
At the end of the questionnaire, participants were asked if they felt this survey accurately captured their experiences of PEM, and 29.8% felt the survey was very accurate, 57.7% reported it was accurate, 10.7% were neutral, 1.2% thought it was not accurate, and 0.1% said it was not at all accurate.
The objective of this study was to use community-based participatory research in an effort to develop a comprehensive way to assess PEM. Based on the comments and items suggested from patients, the following specific aspects of PEM were found to be the most critical domains: the timing of PEM onset, triggers of PEM, symptoms that are exacerbated following exertion or exposure to triggers, phrases used to describe consequences of PEM, duration of PEM, relationship between exertion and length of recovery, and the importance of considering personal characteristics (e.g., how long the patient has had ME/CFS, the course of their illness, their level of functioning, and coping methods used). The patient perspective provided the authors with the critical information to develop this survey of PEM. Of the patients who took part, 87.5% felt that the resulting survey was either very accurate or accurate.
Onset of symptom exacerbation after exertion was found to vary between patients. As shown in Table 2
, the majority of patients experienced both immediate and delayed onset of PEM, and the extent of the delay of symptoms varied considerably. In addition to the unpredictability of PEM onset, several factors affect the duration of PEM before recovery, including the type, intensity, frequency, and duration of the exertion (see Table 6
). These findings are consistent with patients’ reporting of prolonged recovery from PEM symptoms. In one study in which patients and healthy controls participated in a fatiguing exercise test, the patient group’s recovery was prolonged [21
]. In addition, VanNess et al. [13
] found patients with CFS, in comparison to healthy controls, take considerably longer to recover after completing a maximal cardiopulmonary exercise test the next day and a week later. Our findings are also consistent with a study by Chu et al. [11
] who found that when comparing PEM symptom onset between those with ME or CFS to healthy controls, 87‒95% of controls had recovered within 24 h after completing an exercise test. Among those with ME and CFS, PEM symptoms peaked at 24 to 48 h later, and 45‒60% still experienced symptoms up to 5 days later.
Our survey also assessed specific triggers that bring on symptom exacerbation. The effects of physical and cognitive exertion on PEM have been well-established [13
] and these findings are consistent with the current study. For example, only 37% of subjects reported being able to exercise “a little” without PEM-related symptoms, as long as they stay within “certain limits” (see Table 3
). Furthermore, basic activities of daily living (e.g., getting dressed, cooking a meal, bathing), positional changes (e.g., going from lying down to standing up), and emotional stress lead to exacerbation in 78.2%, 64.5%, and 93.2% of patients, respectively.
Another issue explored involved whether there are precipitants of PEM beyond physical or cognitive exertion. The highest reported triggers in addition to physical/cognitive exertion were emotional events (88.3%), noise (85.3%), and sensory (83.6%) and visual overload (79.7%). This is consistent with past literature reporting these types of stimuli as exacerbating symptoms [24
]. It has also been hypothesized that exposure to mold could trigger illness onset and PEM symptomology [25
]. In our sample, 39.4% reported mold triggering their PEM. This is consistent with findings by Brewer, Thrasher, Straus, Madison, and Hooper [26
], where 30% of patients with ME and CFS were reported to have multiple mycotoxins present in their bodies.
Partly as a function of this survey and the interactions with the patient community, there have been several additional developments in the assessment of PEM. First, Cotler et al. [27
] found that use of the 5 recommended PEM DSQ items was an excellent screen in identifying PEM in patients with ME and CFS. In addition, as a second step in the process of assessing PEM, 5 additional DSQ items (including the assessment of duration of symptoms) were successfully used to differentiate PEM from other chronic illnesses. In addition, the findings from the patient survey reported on in this article were revised in order to construct a briefer, more concise measure of PEM, which was significantly related to physical functioning [28
There are several limitations to this study. First, we did not obtain confirmation of ME or CFS diagnoses by independent medical personnel. In addition, we do not know what case definitions, if any, were used in their diagnoses. In addition, consistent with other ME and CFS studies, the sample was not demographically diverse. However, having a sample from several geographic regions did increase the generalizability of findings. Another limitation of the study was the length of the questionnaire. Though participants were presented with the option of pausing, it is reasonable that some may have still found it difficult to complete.
The open, participatory nature of this study provided a unique way of both designing the survey and gathering comprehensive information from the ME and CFS community regarding PEM. There are unique benefits that can accrue to the research and patient community by actively collaborating on instrument development as well as other policy issues, such as the selection of a name for the illness as well as the case definition [29
]. By collaborating with the ME and CFS community, we have provided a model of community-based participatory research, which has multiple advantages to both the patient and research communities [30
]. We close with this quote regarding what needs to occur to further this type of collaborative research in the ME and CFS areas:
“An alternative vision is still possible if those in power are willing to bring all interested parties to the table, including international representatives, historians on the science of illness criteria, and social scientists adept at developing consensus. In a collaborative, open, interactive, and inclusive process, issues may be explored, committees may be charged with making recommendations, and key gatekeepers may work collaboratively and transparently to build a consensus for change. Involve all parties—patients, scientists, clinicians, and government officials—in the decision-making process [31