Definition of Recovery in Chronic Fatigue Syndrome
Authors: David S. Bell MD, FAAP Associate Clinical Professor of Pediatrics, State University of New York at Buffalo David E. Bell, MPH Department of Medical Anthropology, State University of New York at Buffalo
Key Words: Myalgic Encephalomyelitis, Chronic Fatigue Syndrome; Prognosis
Abstract
The definition of clinical recovery has long been debated in myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS).
Clinically, many persons who have had ME/CFS declare themselves "recovered" or "nearly recovered" while continuing to present for medical care because of ongoing somatic symptoms. In this study ten persons who considered themselves "recovered" or "nearly recovered" were given questionnaires to assess health status and compared to healthy adults.
Half of the "recovered" subjects would be considered ill with CFS based upon the disability requirements of the CDC empiric definition of CFS, and all "recovered" subjects had significant somatic symptoms.
Yet these subjects had all returned to normal in the symptom of orthostatic intolerance so that their daily activity was normal.
Thus the perception of recovery in ME/CFS is related to the ability to sustain upright activity and not related to the degree of somatic symptoms, including fatigue.
Introduction
In 1985, a cluster of ME/CFS occurred in Upstate New York involving 210 persons, 60 of whom were children or adolescents. The cluster was located in a 180 square mile rural region located between (but did not include) Rochester and Buffalo, New York. Based on the symptoms of the first 100 patients, diagnostic criteria were published(1), but with the publication of the Holmes criteria(2), it became clear that this cluster was the same as what was being termed chronic fatigue syndrome.
The children involved in this outbreak were a subject of particular attention. Of interest, the proportion of ill children to adults was similar to that of other community-wide epidemics described previously(3, 4). Because adolescents have lower Epstein-Barr virus (EBV) seropositivity, it was possible to eliminate EBV as the cause of this outbreak(5), a hypothesis prevalent at the time. Seventy-five percent of the children ill in this outbreak met criteria for fibromyalgia syndrome(6).
This cohort of children and adolescents with ME/CFS has now been followed clinically for twenty- five years. Four subjects have developed malignancy, and many have tested positive to the gammaretrovirus XMRV, a subject to be described in detail in subsequent studies. In 1995 a follow-up study was published(7) which demonstrated that 80% of those children and adolescents who became ill in 1985 considered themselves "well". However of those 80%, half were doing well despite ongoing somatic symptoms, while the other half had minimal or no somatic symptoms. Twenty percent of the subjects in that study were very ill and disabled. A full study detailing the current health status will be presented under separate cover. In the course of clinical practice and primary care, many of these persons have stated that they have "recovered" or "nearly recovered". However, they continue to present with symptoms suggestive of ME/CFS. The definition of recovery has been difficult to address because of the non-specificity of the symptoms. Current criteria for the diagnosis of CFS, the CDC empirical case definition(8) has one section that specifies degree of disability based upon the Medical Outcomes Survey Short Form-36(9). It has been noted that patients who report themselves "recovered" or "nearly recovered" may have low scores on this instrument. The present study was undertaken to further examine this aspect of the definition of recovery in CFS. The current study was stimulated by CFS patients who have stated that they are "recovered", yet on clinical evaluation and questionnaire are demonstrated to have persistent symptoms.
Methods - Subjects
Ten adults followed clinically for many years with CFS had stated that they had either "recovered" or "almost recovered." To assess the degree of recovery, questionnaires were administered to assess the current severity of somatic symptoms and orthostatic intolerance. Institutional Review Board approval was obtained through the Medina Memorial Hospital Ethics Committee, and all subjects signed informed consent prior to questionnaire administration. No subject in this study had developed malignancy nor alternative causes for fatigue over the twenty-five years since being diagnosed with ME/CFS. Ten healthy adults also completed the same questionnaires.
Methods - Instruments:
a) Hours of Activity Scale: This scale is a measure of orthostatic intolerance; it asks the subject to estimate the average total number of hours of "upright activity within an average 24 hour day." Healthy subjects consistently describe more than 12 hours of upright activity in a day. Severe CFS patients experience 2 or less hours per day, moderate CFS experience 3 to 7 hours, and mild CFS have 8 to 10 hours of upright activity within a 24 hour period (unpublished observations).
b) Visual Analog Scale of 9 Symptoms. This self-rated severity scale from 0 (no symptom) to 10 (very severe symptom) measures fatigue, sore throat, lymph node pain, headache, muscle pain, joint pain, sleep disturbance, memory and cognitive symptoms, and post-exertional malaise, all common symptoms of ME/CFS.
c) Fisk Fatigue Impact Scale (FIS) (10). This instrument is scored from 0 (no impact) to 4 (severe impact) for each of sixty questions. It is designed to assess the impact that fatigue has on daily activity. The maximum score is 160.
d) Bell Activity Scale (11, 12). This scale combines somatic symptoms with activity restriction. Persons score themselves from 0 (bed bound with very severe symptoms, requiring assistance for daily living) to 100 (full and vigorous activity with no significant symptoms). This is a simple and rapid assessment of ME/CFS severity for use at clinic visits (unpublished observations). A copy of this one page questionnaire is attached as an appendix and may be freely used.
e) Short Form-36 (9). Also called the Rand-36, this thirty-six item questionnaire has extensive use in evaluating general health and health perceptions in CFS(13, 14). It is also used to help determine diagnosis in the most recent CDC empiric criteria (8).
Results
The first question of the MOS-36 is a general rating of health status. All ten subjects in this study rated themselves as either "good" or "very good," confirming the perception that they viewed themselves as either "recovered" or "almost recovered". No subject, other than control subjects, rated themselves as "excellent."
Patients who were "recovered" were quite different from healthy controls in three areas: VAS, Ability Scale and FIS. For the Visual Analog Scale, mean recovered CFS score was 19.8 +/- 14.67 while the mean control subject score was 6.1 +/- 4.63. This mean difference is significant at the 0.05 alpha level (p=0.011). For the FIS, mean recovered score was 22.8 +/- 25.83, and the mean control score was 4 +/- 5.81. This difference is significant with a p-value of 0.038. Mean scores for the Bell Ability scale were 99 +/- 3.16 for recovered and 90 +/-12.47 for controls. This was significant with a p value of 0.040. Scores for the MOS-36 will be presented under separate cover.
However, the two groups did not differ in the hours of activity scale. Recovered CFS subjects had a mean of 14 +/- 1.94 hours of upright activity, while control subjects had 15.5 hrs +/-1.67 hours of upright activity. The average difference of the means proved to be not statistically significant (p=0.080). The data is presented in Table 1.
Discussion
The results of this small study suggest that all of ten persons who, in clinical follow-up had stated they had either "recovered" or "almost recovered" had persistent symptoms on several questionnaires. In fact, if the MOS-36 scores are used as an index of disability as suggested by the CDC empirical case definition(8), five of the ten "recovered" subjects would still meet criteria as having CFS.
Comparing the ten "recovered" subjects to the healthy controls, clear differences were seen in visual analog scores, Bell Ability Scale, and the Fatigue Impact Scale scores. Of these three, the least significant scores were seen in the Ability scale, perhaps because this scale attempts to combine orthostatic intolerance with somatic symptoms.
However, the Hours of Activity Scale scores, a measure of orthostatic intolerance, were the same in the two groups. This implies is that the perception of recovery is based on the symptom of orthostatic intolerance and is independent of somatic symptoms. That is, when persons with CFS improve and reach a point where they can sustain upright activity for more than twelve hours in a day, they perceive themselves as "recovered" or "almost recovered", despite the fact that other somatic symptoms remain. This observation has relevance in the definition of recovery in ME/CFS, an illness that has no clearly defined biologic markers at present. If confirmed in larger studies, it may explain the large discrepancy in recovery rates in studies of ME/CFS. Thus, future studies of the natural history of the illness will need to discriminate between somatic symptoms and overall activity. It may be that after a number of years, persons with ME/CFS adjust to ongoing somatic symptoms. And if they return to normal activities with improvement of orthostatic intolerance, they perceive themselves as "recovered", when in fact only one aspect of their illness has improved. Again, if this is confirmed, it implies that full recovery from ME/CFS is exceedingly rare. One specific concern related to the definition of recovery in ME/CFS is that when people consider themselves recovered, they feel able to donate blood. One "recovered" subject in this study had normal activity but significant somatic symptoms and was a regular blood donor. Recently the gammaretrovirus XMRV has been implicated in persons with CFS(15). While the relationship of XMRV and ME/CFS is still under debate, these findings carry important implications. Furthermore, it should be remembered that only 20% of persons with ME/CFS receive a diagnosis of CFS from their health care provider (16). A further possible implication of the uncertain definition of recovery in ME/CFS is the interpretation of XMRV incidence in the healthy control population. It will be important in the future to inquire if subjects have ever had a CFS-like illness in the past.