CFS patients have an unusual complaint – that even minimal exertion produces a dramatic worsening of their entire symptom complex beginning a day or two later. However, very little work has focused on the scientific validation of this complaint. In our previous work, we showed that activity as monitored by actigraphy diminished but not until 5 days after the period of exertion (8
). Importantly, the present follow-up study, focusing on symptoms, showed the same effect. Physical symptoms did not change following exertion until 5 days later. This prolonged delay appears strikingly different from the sort of post-exertional symptom worsening that occurs in cardiopulmonary disease. This delay may distinguish CFS from other fatiguing illnesses. In addition, psychological symptoms did not get worse over time. This dissociation between physical and psychological symptoms is important because it suggests that physical symptom worsening is not associated with altered mood.
We believe that a major reason we were able to capture this delay relates to our use of a cEMA technique. Subjects were asked to provide information about symptoms repeatedly throughout the day and across many days, and responses had to be made at the time of query. Doing this allows for two important differences from paper and pencil diaries: first, time-stamped data assures they represent the patient’s actual response at that particular time, and second, providing repeated input as to symptoms should give more reliable data to assess for change over time.
Finding a prolonged period between the time of exertion and the symptom exacerbation raises questions of mechanism. The cause of this delayed worsening in physical symptoms may attributable to some immunological change in CFS patients (17
). In particular, Cannon et al. (18
) reported that plasma α2-macroglobulin concentrations in CFS patients were significantly higher than those of control subjects on four of the five days after exercise, and these changes might be associated with the delayed worsening in physical symptoms. In addition, impaired hypothalamo-pituitary-adrenal axis may contribute to the symptoms (19
An earlier momentary assessment study done on CFS patients doing their usual activities (20
) noted that fatigue and arousal were worst early and late in the day for both patients and controls with patients having worse symptoms across the day. Our data were similar to the earlier report in the point that physical symptoms were less severe in the afternoon. In addition, both patients and controls had more psychological symptoms in mornings and afternoons than in nights with the patients having higher scores on these symptoms across the entire day. As was the case for physical symptoms, the CFS group showed less variability of psychological symptoms across the entire day. This diurnal pattern of psychological symptoms was also similar to those in earlier studies (20
In contrast to increased physical symptoms after exercise, cognitive function did not deteriorate over time although many studies have reported impairment in cognitive function at baseline (22
) or after exercise (11
) for patients with CFS. The reason for this discrepancy may relate to our use of the continuous performance test in this study although one of our previous studies showed that exercise did not alter cognitive function (26
). Another possible reason is the time when cognitive tests were performed. In many previous studies, cognitive tests were performed just after exercise while tests were done for a longer period in this study.
There were some limitations in this study. First, the sample size was relatively small and there was some loss of data in the second week after exercise, which might cause difficulty in generalizability of the result in the present study. Therefore, further studies with a larger sample size for a longer period are needed to confirm the results of this study. Second, the subjects in this study were only women. Therefore, it is not possible to apply the results of this study to men with CFS. Third, objective activity was not measured in this study. Therefore, the relationship between subjective symptoms and objective activity remains unknown. Finally, the regression coefficient of the GROUP × DAY2 interaction was not so large compared with the main effect of the GROUP in the model for the physical symptoms. Therefore, the clinical significance should be interpreted with caution.
Nonetheless the results, using an EMA technique, are clear: CFS patients showed worsening of physical symptoms beginning 5 days after performing a standard exercise test to volitional exhaustion; in contrast, exercise did not adversely affect psychological symptoms or cognitive performance. These findings suggest that symptom exacerbation is not a function of altered mood. Documenting symptom worsening itself and the delay preceding it is important in that it provides an outcome measure for therapeutic trials. Moreover, its existence may be useful in moving the diagnosis of CFS from patients’ complaint to objective measures of altered function.