Cohort Stratification

Research into myalgic encephalomyelitis as a distinct disease necessitates verifying patients have been thoroughly screened using the 2011 International Consensus Criteria (Carruthers et al). Further confirmation of an ME diagnosis requires ruling out conditions that may be mistaken for ME.

The ME IC Primer offers clear guidance on screening for ME.

In addition, other factors have been found to be important for stratifying patients in order to reach repeatable results.

Research stratification:

  • Fulfills the ME International Consensus Criteria (ME ICC)
  • Cohort screened for often overlooked diagnosis, like multiple sclerosis.  See our Conditions to Rule Out info sheet.
  • Gender
  • Disease onset (sudden or gradual)
  • Length of time ill (before or after 5 years is an option)
  • Age
  • Disease severity
  • Pre- and Post-menopause

Over the years, other patient groups have been lumped under the CFS and ME/CFS label.

Chronic Fatigue Syndrome (Fukuda)
1994 – clinical and research criteria. This criteria was vague and did not require the cardinal symptom of post exertional malaise. Research using this criteria needs to be duplicated to confirm it applies to ME.

Canadian Consensus Criteria (CCC)
2003 – clinical criteria. Because CFS-Fukuda was recognized as being far too broad for research, many researchers used the CCC for patient selection.

WE RECOMMEND using the ME International Consensus Criteria (ICC) LINK
2011 – clinical and research criteria. This criteria along with the ME Adult & Paediatric International Consensus Primer for Medical Practitioners provides guidance to select a more specific patient set.

From the ME IC Primer (pg ii): “Patients diagnosed using broader or other criteria for CFS or its hybrids (Oxford, Reeves, London, Fukuda, CCC, etc.) should be reassessed with the ICC. Those who fulfill the criteria have ME; those who do not would remain in the more encompassing CFS classification.”

Examples of research using ME International Consensus Criteria for patient selection.
Examples of research using ME Canadian Consensus Criteria for patient selection.

See our Understanding Criteria page for more information.

Some examples of research showing the importance of stratification

Revisiting IgG Antibody Reactivity to Epstein-Barr Virus in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Its Potential Application to Disease Diagnosis   24 June 2022
“Thus, given the heterogeneous nature of ME/CFS, it is pivotal to stratify patients adequately, based on age, gender, and disease trigger for biomarker discovery.”  “An implication of having a different antibody profiling between men and women is that analysis of each gender should be performed separately.”

Survey of Anti-Pathogen Antibody Levels in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome   10 June 2022
“While most of the differences were not significant, the opposite trends between male and female antibody levels indicate it is inappropriate to combine data from the two sexes. … Age-based cohort stratification provides additional insight into humoral immune biology, with a large number of antigens identified with significantly different antibody levels between subjects under 50 and those over 50. ..”

Volumetric differences in hippocampal subfields and associations with clinical measures in myalgic encephalomyelitis/chronic fatigue syndrome   31 March 2022
“Our study found left hippocampal subiculum, presubiculum, and fimbria volumes were significantly larger in ME/CFSICC patients compared with HC, but not for ME/CFSFukuda patients. Furthermore, this study demonstrated that multiple hippocampal subfield volumes are different in ME/CFSICC patients meeting the strict ICC case definition, and they exhibited strong associations with clinical measures. Therefore, the strict case definitions are essential in investigation of the pathophysiology of ME/CFS. Subiculum and parasubiculum volumes were larger in ME/CFS in contrast to reductions seen in other neurological disorders.”

NOTE: Some research uses the label ME/CFS, CFS/ME or CFS. Selection of patients using the ME-ICC is most accurately labeled myalgic encephalomyelitis.