Various physical findings

Betsy Keller (Ithaca College, NY) described Cardio-Pulmonary Exercise Testing, pointing out that it is the most reliable and repeatable measure of functional ability in ME/CFS. She also pointed out that results do not change significantly in normal individuals who are tested and then re-tested 24 hours later. However, in PWCs the aerobic capacity  (VO₂ max), work load, heart rate, and other measures fall more than 8%, confirming the clinical impression post-exertional malaise. She pointed out that many PWCs function at very low levels (say 2-3 METS at their Anaerobic Threshold) and that it takes 1.3 METS to just sit, 1.8 METS to sit and read or write, and 3 METS to just stroll leisurely at the mall. Most activities of daily living require at least 3-5 METS, which explains why patients struggle to keep up at home.

Chris Snell (University of the Pacific, Stockton) and his group have done much to promote Cardio-Pulmonary Exercise Testing as a measure of impairment and post-exertional malaise. Today the Stevens Test-Retest Protocol is widely used for disability purposes, and was named after one member of the team, Staci Stevens. Snell pointed out that regression equations are used to estimate the aerobic work capacity and anaerobic threshold following indirect estimations of work ability (treadmill test, 6-minute walk, 1.5 miles-for-time), but are notoriously inaccurate due to assumptions made. Only exercise testing with expired gas testing is accurate. Snell also pointed out that the notorious British PACE Trial used the 6-minute walk test as a measure of improvement. At baseline, subjects walked an average of 312 meters in 6 minutes, and after 52 weeks of training they could walk 379 meters, a 21% improvement. This sounds wonderful until you realize that this is the equivalent of walking 2.35 mph (instead of 1.94 mph) for 6 minutes, or about 2 METS—still in the severely disabled category after a year of work!

Ian Treaseden (Imperial College, London) used voxel-based MRI studies to show that white and gray brain matter was decreased in PWCs in their occipital lobes (which control balance), left angular gyrus (affects perceptual sequence learning, action awareness, movement consequences), and the left hippocampal gyrus (which encodes and retrieves memory). These changes can explain many of the balance and cognitive difficulties seen in PWCs, and argue strongly for an organic basis in ME/CFS. Treaseden reassured us, however, that these changes are not permanent.

Many symptoms of CFS and can be attributed to autonomic system dysregulation, poor sympathetic nervous system control, and/or low blood volume. The latter would reduce stroke volume or cardiac output from the heart. Roumiana Boneva (CDC, Atlanta GA) investigated the possibility that low aldosterone levels lead to low blood volume in ME/CFS. Studying 69 PWCs and 212 controls, Boneva showed that the mean aldosterone was 4.46 in ME/CFS and 6.05 in controls. Neither of these is terribly low, but significantly different (OR = 1.65). The cause is unknown.

[Ed. note: this study confirms the similar study by Bell and Streeten many years ago. Also, the CDC Witchita Study showed that renin is elevated as a regulatory response to low aldosterone.]

Changing gears, Ekua Brenu, a young PhD candidate and very active researcher from Queensland AU, studied cytotoxic function and markers in PWCs at 6 month intervals to determine the stability of these observations over time. She confirmed that suppression of NK-cells (CD56) was the most reliable finding, and could be a potential biomarker for ME/CFS. On the other hand, a number of other markers (TH-1, TH-2, TH-17 cytokines, IL-1α, IL-1β, and TGF-β) varied over time.