ME/CFS Study: EEG spectral coherence data distinguish chronic fatigue syndrome patients from healthy controls and depressed patients - A case control study

You have to hand it to Anthony Komaroff, he makes sure that his work is solid (even if that means moving the research ahead a bit slower...). Not only did he enroll 70 patients with ME/CFS (which already is a lot) and 24 patients with major depression, but furthermore he enrolled 148 (!) patients with "general fatigue" (not evaluated whether they meet CDC/Fukuda) and 390 (!) healthy controls.

EEG spectral coherence data distinguish chronic fatigue syndrome patients from healthy controls and depressed patients - A case control study
Abstract (provisional)

Frank Duffy, Gloria McAnulty, Michelle McCreary, George Cuchural and Anthony Komaroff

Background
Previous studies suggest central nervous system involvement in chronic fatigue syndrome (CFS), yet there are no established diagnostic criteria. CFS may be difficult to differentiate from clinical depression. The study's objective was to determine if spectral coherence, a computational derivative of spectral analysis of the electroencephalogram (EEG), could distinguish patients with CFS from healthy control subjects and not erroneously classify depressed patients as having CFS.

Methods
This is a study, conducted in an academic medical center electroencephalography laboratory, of 632 subjects: 390 healthy normal controls, 70 patients with carefully defined CFS, 24 with major depression, and 148 with general fatigue. Aside from fatigue, all patients were medically healthy by history and examination. EEGs were obtained and spectral coherences calculated after extensive artifact removal. Principal Components Analysis identified coherence factors and corresponding factor loading patterns. Discriminant analysis determined whether spectral coherence factors could reliably discriminate CFS patients from healthy control subjects without misclassifying depression as CFS.

Results
Analysis of EEG coherence data from a large sample (n=632) of patients and healthy controls identified 40 factors explaining 55.6% total variance. Factors showed highly significant group differentiation (p<.0004) identifying 89.5% of unmedicated female CFS patients and 92.4% of healthy female controls. Recursive jackknifing showed predictions were stable. A conservative 10-factor discriminant function model was subsequently applied, and also showed highly significant group discrimination (p<.001), accurately classifying 88.9% unmedicated males with CFS, and 82.4% unmedicated male healthy controls. No patient with depression was classified as having CFS. The model was less accurate (73.9%) in identifying CFS patients taking psychoactive medications. Factors involving the temporal lobes were of primary importance.

Conclusions
EEG spectral coherence analysis identified unmedicated patients with CFS and healthy control subjects without misclassifying depressed patients as CFS, providing evidence that CFS patients demonstrate brain physiology that is not observed in healthy normals or patients with major depression. Studies of new CFS patients and comparison groups are required to determine the possible clinical utility of this test. The results concur with other studies finding neurological abnormalities in CFS, and implicate temporal lobe involvement in CFS pathophysiology.

Over at ME/CFS forums, Forbin has made this observation:

For part of the study, they also recruited patients who complained of prolonged, unexplained fatigue (with other conditions ruled out) but who had never been worked up for CFS. About 45% of those people had results consistent with the CFS group. The paper suggests that this is broadly consistent with a previously published estimate that 35% of such a group might be expected to be classified with CFS. They speculate that “the less than 100% accuracy of our spectral coherence based classification function could reflect a deficiency in the CDC criteria for CFS...”

So it seems to me that at least a one third of "significantly fatigued patients (where no underlying diagnosis can be securely established)" (sfP) suffer from "genuine" ME/CFS – and up to two third of sfP might have something different (or might be patients with ME/CFS who are less symptomatic).

90% of patients with CDC-CFS (diagnosed by Komaroff?) have abnormal EEG. So in the right hands (and with a large enough cohort) the CDC criteria aren't so bad for research (up to 10% false positive and no false negatives), but might be better suited for clinical diagnoses than research.


From what I have read so far, I have a feeling the CCC might reject some patients with "genuine" ME/CFS (and not include false positives) and so might be better for research, especially when in the hands of less experienced researchers... It would be nice if they would do something like this: "xx% of our CFS-subjects qualified for both CDC and CCC. Hindsight analysis showed that CCC improved specificity to yy%, but decreased sensitivity to zz%. ..."