Review of the Two-day Exercise Test with a Pediatric Case Report
David S. Bell, M.D.
In the most recent Journal of Chronic Fatigue Syndrome (Vol 14, Number 2, 2007) there are two articles which may be the first to offer an objective proof of disability in ME/CFS. More importantly, if shown to be correct, they may give us an avenue to test and measure the biochemical abnormality which causes the symptom pattern. In this short review I would like to review these two papers and present a case of pediatric CFS which demonstrates the same abnormalities.
In the first of these papers, Margaret Ciccolella, a lawyer, teams up with Staci Stevens, Chris Snell, and Mark Van Ness of the University of the Pacific to review the legal issues surrounding exercise testing and disability (1). As everyone familiar with CFS well knows, insurance companies require proof of disability, and a standard exercise test may or may not demonstrate disability at a sedentary level. However, even if disability is present, insurance companies have been quick to say that the patient was not trying hard enough, or that the patient is de-conditioned. The second paper of this series by VanNess, Snell and Stevens explain the two-day exercise test and presents results for six patients with ME/CFS (2).
As clinicians have observed, the symptom of “post-exertional malaise” is one of the most distinguishing features of CFS. This symptom is listed as one of the eight in the criteria of the Centers for Disease Control (3), and is central to the diagnosis in the recent Canadian Case Definition (4) and the proposed pediatric case definition (5). It is beginning to look like the symptom of post-exertional malaise is at the root of disability, and may be central to the pathophysiology of this complex illness spectrum.
A person with ME/CFS may be at home for several days doing little except basic activities of daily living. When this patient decides to go shopping, he or she will drive to the mall and shop for one or two hours. During this time, observers would say that the person looks entirely well, not appearing disabled. However, following this activity the patient will experience an exacerbation of pain and other symptoms of ME/CFS. This exacerbation may last one, two or three days, and, in my opinion, the more severe the illness, the longer and more severe the exacerbation. This phenomenon is known as post-exertional malaise. The symptoms of the illness (malaise) are exacerbated by mental, physical or emotional activities (post-exertional). In an employment environment, the patient may be able to do a job well for one or even several days. However disability lies in the inability to sustain this normal level of activity. The two-day exercise test is the first to begin to explain this phenomenon.
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The exercise test is no different from what has been used for years. The patient exercises on a stationary bicycle (bicycle ergometry) and breathes through plastic tubing to measure oxygen and carbon dioxide. The six female patients and six sedentary matched control subjects of the study were all able to achieve maximal exertion. The ME/CFS patients had a slightly lower V02max (maximal oxygen utilization) than controls (28.4 ml/kg/min vs. 26.2 ml/kg/min) and lower VO2 at anaerobic threshold (15.01 ml/kg/min vs. 17.55 mg/kg/min) on the first day of exercise testing. These values are not dramatic nor are they statistically significant. It is on the second day that interesting results are seen.
The same test was repeated the following day for all twelve subjects. As is often the case, sedentary controls improved slightly in their ability to utilize oxygen, going from 28.4 to 28.9 ml/kg/min for VO2max and from 17.55 to 18.00 ml/kg/min for oxygen utilization at anaerobic threshold. The CFS patients however worsened in both categories: VO2max fell 22% from 26.23 to 20.47 ml/kg/min, and oxygen utilization at anaerobic threshold fell 27%, from 15.01 to 11.01 ml/kg/min. To put it into perspective, these values are in the severe disability range on the American Medical Association guidelines.
Sedentary or de-conditioned persons do not change their oxygen utilization because of an exercise test. Even patients with heart disease, cystic fibrosis or other diseases do not vary more than 7% from one day to the next. However, the patients with ME/CFS in this study had a significant drop; something occurred because of the test on the first day interfered with their ability to utilize oxygen on the next day. And this is exactly what patients with ME/CFS have been describing with the symptom of post-exertional malaise. As the authors state, “The fall in oxygen consumption among the CFS patients on the second test appears to suggest metabolic dysfunction rather than a sedentary lifestyle as the cause of diminished exercise capacity in CFS.”
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Case Report: JAD developed widespread musculoskeletal pain and fatigue at the age of sixteen following a flu-like illness. Past history included learning disabilities during the early grades and treatment with psychostimulants with subsequent development of tic disorder which resolved. Because of the severity of symptoms and inability to attend school with the onset of ME/CFS, he underwent an extensive medical evaluation. Abnormalities included twelve fibromyalgia tender points on physical examination; decreased circulating blood volume of 32 mL/Kg (normal 55-75 mL/Kg) with symmetric contractions in both red cell and plasma volume; serum cortisol on one occasion was elevated at 38.1; postural orthostatic tachycardia was present on tilt table testing.
Results from two-day exercise testing were as follows: On day 1 VO2max was 41.2 ml/kg/min, indicating a mild functional impairment. On the second day, peak oxygen consumption (VO2max) was 33.3 ml/kg/min; VO2 at anaerobic threshold on day 1 was 24.6 ml/kg/min and on day 2 was 16.1 ml/kg/min. The results demonstrate low oxygen consumption at anaerobic threshold and at peak workload, significantly worse on the second day of exercise testing.
Conclusions: The results of the two-day exercise testing are objective and not dependent upon subjective symptoms. Moreover hypochondriasis, intentional falsification, and/or poor effort can be detected by the physiologic parameters. Therefore the two-day exercise test, if confirmed in a larger trial, could become a clinical trial end point. More importantly, evaluations could be designed which would demonstrate the specific metabolic abnormality generated by the exercise of day one and demonstrated on the second day exercise test. It would be my hope that these findings be explored without delay.
1. Ciccolella M, Stevens S, Snell C, VanNess J: Legal and Scientific Considerations of the Exercise Stress Test. JCFS 2008, 14(2):61-75.
2. VanNess JM, Snell CR, Stevens S: Diminished Cardiopulmonary Capacity During Post-Exertional Malaise. JCFS 2008, 14(2):77-85.
3. Fukuda K, Straus S, Hickie I, Sharpe M, Dobbins J, Komaroff A, Group ICS: The chronic fatigue syndrome: a comprehensive approach to its definition and study. Ann Intern Med 1994, 121:953-959.
4. Carruthers B, Jain A, DeMeirlier K, Peterson D, Klimas N, Lerner A, Bested A, Flor-Henry P, Joshi P, Powles ACP et al: Myalgic encephalomyelitis/chronic fatigue syndrome: Clinical working case definition. diagnostic and treatment protocols. J Chronic Fatigue Syndrome 2003, 11(1):1-12.
5. Jason L, Bell D, Rowe K, Van Hoof E, Jordan K, Lapp C, A G, Miike T, Torres-Harding S, De Meirleir K. A Pediatric Case definition for myalgic encephalomyelitis and chronic fatigue syndrome. J CFS 2006, 13:1-44
Address all correspondence on this article to David S. Bell at dsbellmd@yahoo.com.
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