Recovery from Exercise in Persons with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Abstract

Background and Objectives: Post-exertional malaise (PEM) is the hallmark of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), but there has been little effort to quantitate the duration of PEM symptoms following a known exertional stressor. Using a Symptom Severity Scale (SSS) that includes nine common symptoms of ME/CFS, we sought to characterize the duration and severity of PEM symptoms following two cardiopulmonary exercise tests separated by 24 h (2-day CPET). Materials and Methods: Eighty persons with ME/CFS and 64 controls (CTL) underwent a 2-day CPET. ME/CFS subjects met the Canadian Clinical Criteria for diagnosis of ME/CFS; controls were healthy but not participating in regular physical activity. All subjects who met maximal effort criteria on both CPETs were included. SSS scores were obtained at baseline, immediately prior to both CPETs, the day after the second CPET, and every two days after the CPET-1 for 10 days. Results: There was a highly significant difference in judged recovery time (ME/CFS = 12.7 ± 1.2 d; CTL = 2.1 ± 0.2 d, mean ± s.e.m., Chi² = 90.1, p < 0.0001). The range of ME/CFS patient recovery was 1-64 days, while the range in CTL was 1-10 days; one subject with ME/CFS had not recovered after one year and was not included in the analysis. Less than 10% of subjects with ME/CFS took more than three weeks to recover. There was no difference in recovery time based on the level of pre-test symptoms prior to CPET-1 (F = 1.12, p = 0.33). Mean SSS scores at baseline were significantly higher than at pre-CPET-1 (5.70 ± 0.16 vs. 4.02 ± 0.18, p < 0.0001). Pharmacokinetic models showed an extremely prolonged decay of the PEM response (Chi² > 22, p < 0.0001) to the 2-day CPET. Conclusions: ME/CFS subjects took an average of about two weeks to recover from a 2-day CPET, whereas sedentary controls needed only two days. These data quantitate the prolonged recovery time in ME/CFS and improve the ability to obtain well-informed consent prior to doing exercise testing in persons with ME/CFS. Quantitative monitoring of PEM symptoms may provide a method to help manage PEM.

Keywords: 2-day cardiopulmonary exercise test; chronic fatigue syndrome; exercise recovery; myalgic encephalomyelitis; post-exertional malaise; specific symptom severity.

Figure 1

Visual Analogue/Likert Scores of Symptoms.

Figure 2

Mean score of all nine domains of the SSS instrument—ME/CFS subjects only. The shaded area represents the 95% confidence interval. Note that there are a significant number of data points beyond day 10, representing about 7–8% of ME/CFS subjects. Each dot is the mean SSS score for an individual ME/CFS subject; Blue line is the spline curve representing the average of all data points in the figure; Light blue area is the 95% confidence interval.

Figure 3

Post-Exertional Malaise (PEM) domain score of SSS instrument—ME/CFS vs. CTL. The shaded area represents the 95% confidence interval. Each dot represents the PEM score for a single subject; Blue dots are low scores, red dots are high scores; Black lines represent the spline curves for group averages; Grey shaded areas are the 95% confidence intervals.

Figure 4

Fatigue domain score of SSS instrument—ME/CFS vs. CTL. Shaded area represents the 95% confidence interval. Each dot represents the PEM score for a single subject; Blue dots are low scores, red dots are high scores; Black lines represent the spline curves for group averages; Grey shaded areas are the 95% confidence intervals.

Figure 5

PEM domain score of SSS instrument by study site—ME/CFS vs. CTL. Fatigue domains score of SSS instrument—ME/CFS vs. CTL. Each dot represents the PEM score for a single subject; Blue dots are low scores, red dots are high scores; Black lines represent the spline curves for group averages; Grey shaded areas are the 95% confidence intervals.

Figure 6

Post-Exertional Malaise (PEM) Recovery by Level of Baseline Symptoms. PEM domain scores of the SSS instrument by the severity of pre-test symptoms: High, Intermediate (Int) or Low—ME/CFS only. Each dot is the mean PEM score for an individual ME/CFS subject; Blue lines are the spline curves representing the average of all data points in each subgroup; Light blue areas are the 95% confidence intervals.

Figure 7

Oral Dose Pharmacokinetic Model of PEM Response to 2-day CPET. Oral dose pharmacokinetic model of mean SSS score. Pre-test scores were normalized to 0, and on subsequent survey days, all mean SSS scores ≤ 0 were set to 0 as representing full recovery from the 2-day CPET. F ratio = 8.41, p < 0.0005. Black box represents that in this model all subject’s Mean SSS scores were normalized (set to 0 at time 0, or pre-CPET1, for all subjects); Black dots are all other normalized Mean SSS scores for each subject, at subsequent days; Green line is the mathematical solution for the model.

Figure 8

Four Parameter Pharmacokinetic Model of PEM Response to 2-day CPET. Four-parameter pharmacokinetic model of normalized mean SSS scores. Scores were adjusted for pre-test symptoms, such that all pre-test values were 2.45 (open box at day 0). Black box represents that in this model all subject’s Mean SSS scores were normalized (set to 2.45 at time 0, or pre-CPET1, for all subjects); Black dots are all other normalized Mean SSS scores for each subject, at subsequent days; Green line is the mathematical solution for the model.

Figure 9

One-Dose Pharmacokinetic Model by Pre-CPET 1 Symptoms. One dose pharmacokinetic model by pre-CPET1 symptoms—ME/CFS only. High, Intermediate (Int) and Low groups were assigned by their pre-CPET1 mean SSS scores; High and low were the highest and lowest quartiles, Int was the middle two quartiles. Intermediate and high groups were not significantly different from the low group: High group vs. Int, F ratio = 0.05, N.S.; Low, F ratio = 0.01, N.S.; Int group vs. Low: F ratio = −0.04, N.S. Black boxes represent that in this model all subject’s Mean SSS scores were normalized (set to 0 at time 0, or pre-CPET1, for all subjects); Black dots are all other normalized Mean SSS scores for each subject, at subsequent days; Red, green and blue lines are the mathematical solutions for each group in the model.