The Search for a Test (part two*)

By Patti Schmidt

The first part of this story gave readers an overview of some potential diagnostic markers for chronic fatigue syndrome (CFS), including Dr. Robert Suhadolnik’s RNase L enzyme test, Dr. Paul Cheney’s preliminary studies on abnormal “voyager” RNA and Georgetown University’s finding that 5-HIAA, a metabolite of serotonin, may be present in elevated levels in CFS patients. In this second installment we will update you on some other efforts to develop diagnostic tools for CFS.

Subgrouping patients
Researchers from the Collaborative Pain Research Unit at the University of Newcastle in Australia have been studying CFS since 1992. The unique twist to the Newcastle group’s work is that they are attempting to go beyond a simple positive/negative test and actually subclassify patients based on test findings to devise individual patient management plans.

The Newcastle group found that the biochemical profiles of CFS patients vary widely, which is not surprising given that the illness has several possible causes. They speculate that CFS often involves co-morbid diseases such as those seen in HIV/AIDS patients, where the initial viral infection causes a change that makes patients susceptible to other conditions or infections. These co-morbid illnesses can contribute to the complex symptoms of CFS and should be identified and treated separately, they believe.

The group’s tests currently consist of measuring amino acids and organic acids in urine, fatty acids and sterols in blood plasma, and assessing faecal microbiology. They have developed special molecular profiling techniques to take biochemical “snapshots” of cell materials or body fluids and have compiled a database of abnormal laboratory findings that occur in subpopulations of patients. Patients can be compared to subcategories in the database to help identify any disease-related changes or potential for co-morbid conditions.

The Newcastle group emphasizes that testing should be performed after the patient has been clinically evaluated for CFS as recommended by the U.S. Centers for Disease Control. Testing can subclassify patients by amino acid abnormalities or by excretions associated with particular types of pain, based on their tests.

For example, some patients show signs of excessive secretion of certain amino acids, which the Newcastle group believes is indicative of underlying disease or genetic problems. The group has found that cystinuria, a fairly common genetic condition that is indicated in part by high urinary lysine levels (more than 20% of urine sample) occurs four times more frequently in CFS patients. This information can be useful in treatment. While many CFS patients take lysine to inhibit viral production, the group warns that too much of this amino acid is likely to be detrimental to the patient as it could interfere with nitric oxide production and lead to increased musculoskeletal pain levels.

Exercise testing
Another diagnostic testing avenue being explored is exercise capacity. During a cardiopulmonary exercise test, the patient performs some type of physical work, like walking on a treadmill, and the air exhaled is analyzed to determine if the heart, lungs and metabolic systems are operating normally.

A group of researchers from the Univer-sity of the Pacific studied how CFS patients responded to cardiopulmonary testing. The results from the first 59 patients tested were presented in April as a poster at the Experimental Biology Conference in San Diego. Even though the volume of air the patients were able to take in during exercise (VE) was normal, the amount of oxygen from the air that they were actually able to use (VO2) was diminished. In fact, according to the American Medical Association’s guidelines, test subjects showed significantly impaired oxygen consumption levels.

Researchers believe these findings support the idea that the mitochondria inside the patients’ muscle cells, which use oxygen to supply energy to the body, may be damaged. They are currently compiling cardiopulmonary data from a multicenter drug study to compare oxygen utilization values for CFS patients and controls. The exercise capacity study will eventually include 230 patients.
Researchers are currently comparing the results of the exercise tests with other biochemical markers for CFS with the hope of providing patients with another objective marker for documenting disability.

“Classification of functional impairment based on an exercise test seems to correlate well with disease severity in CFS,” said Staci Stevens, MA, one of the lead researchers. “So it is reasonable to suggest that our metabolic data might eventually assist patients in obtaining disability benefits.”

Cardiopulmonary exercise testing is currently used for documenting functional disability for other medical conditions.

More avenues evolving
Several other avenues for diagnostic testing are still in their infancy. For example, the Centers for Disease Control (CDC) is working on a gene expression test for CFS. According to a statement on the agency’s web site, the “CFS program has intentionally emphasized gene expression studies because staff believe this methodology affords the optimal likelihood to identify markers of disease and resolve difficulties with specificity of case definitions.”  (For more on case definition, see "Revision of CFS Case Definition Underway" in this issue.)

CDC scientists are using high density filter arrays and differential display PCR, two cutting-edge technologies, to analyze gene expression in patients’ white blood cells. Results from these studies should provide information on abnormal genetic pathways
and may identify any pathological entities, such as viruses, that might be involved. Samples gathered as part of the CDC’s epidemiological study in Atlanta are now being analyzed, and testing of samples collected in Wichita, Kan., will begin this year.

In addition, a Canadian university student developed a simple blood test in 1998 to measure concentrations of a glucose metabolite in red blood cells that may be a diagnostic tool for CFS. She has won several awards and has been invited to present her findings at two medical conferences. Unfortunately, she could not be reached by the time this issue of the Chronicle went to press to determine whether plans are underway to research this potential test further.

*   The first part of this story appeared in the Winter 2000 issue of the Chronicle.

Patti Schmidt is a former newspaper editor on long-term disability due to CFIDS.  She is also a Board member of The CFIDS Association of America.