A puzzle without a picture (by Schlurcher, Wiki Commons)

A puzzle without a picture (by Schlurcher, Wiki Commons)

One of the most animated debates surrounding ME/CFS concerns the name of the illness and how it is diagnosed. At present, a range of possible definitions exist – around 20 according to a 2014 review, and 21 if we include the new SEID definition from the Institute of Medicine – but each is different (sometimes subtly), and today the terms ME, CFS and their various combinations mean different things to different people. Does this matter? Absolutely – because the different ways of diagnosing patients (‘diagnostic criteria’ in the parlance) capture different kinds of patients, and this, in turn, influences clinical research, the treatment options that are offered, and the perception of the illness by employers, benefit agencies and the public generally.

One of the most commonly discussed definitions is the 2003 ‘Canadian Consensus Criteria’ for ME/CFS. This was designed to help health professionals make a diagnosis effectively but, like most ‘definitions’ of ME or CFS, has never been formally validated, which was why researchers at the Department of Paediatrics, Oslo University Hospital wanted to investigate its clinical usefulness. They examined an unselected group of 120 young people (mean age 15.4 years), all with a minimum of three months of unexplained chronic/relapsing fatigue of new onset, causing disability to a degree that prevented normal school attendance, and sub-grouped the youngsters according to they whether or not they fulfilled the Canadian Consensus Criteria. The two groups were then compared on a wide range of tests, including clinical examination, blood sampling and testing for disease markers (of cognitive, HPA-axis and autonomic function, and inflammatory responses). They also completed an inventory of the frequency and severity of 24 common symptoms of illness during the preceding month.

While the report would have benefited from more detail about the precise sub-classifications of patients meeting the Canadian Consensus Criteria (and about the group of patients who did not, e.g. how close they came to fulfilling the criteria), the results were stark nevertheless. They revealed that disease markers and other outcomes were no different in youngsters who satisfied the criteria (46 patients) than in those who did not (69 patients). In particular, C-reactive protein levels and cytokine expression (which both indicate the presence of systemic inflammation) were similar in both groups. Group differences were found on only one test of cognitive function, which was poorer in the group fulfilling the criteria. Also, activity levels measured by an activPAL accelerometer were similar in both groups over the 30 weeks of the study, after adjustment for baseline differences.

As the researchers explain, their study explores two aspects of ‘content validity’ – discriminate validity (in this case, whether the Canadian Consensus Criteria can define a group of patients that is clinically distinct from the others) and prognostic validity (whether youngsters meeting the Criteria have a significantly different outcome from the others). In neither case was the Canadian Consensus Criteria found to be sensitive, leaving a question mark over its practical usefulness in research or clinical practice.

The aim of the Canadian Consensus Criteria was “to reflect ME/CFS as a distinct entity and distinguish it from other clinical entities that have overlapping symptoms”, and to clarify diagnosis by providing consensus-based standardised diagnostic and treatment protocols. Yet – 12 years on – we still know very little about its usefulness in practice, apart from the fact that 50–60% of patients meeting the wider (and more vague) Fukuda 1994 criteria also meet the Canadian Consensus Criteria and that these patients have a higher burden of illness (see Nacul et al., BMC Med, 2011). While this lack of knowledge reflects the very low level of research into ME/CFS  compared with other chronic illnesses, it also illustrates the importance of clinical studies, like this one from Norway, testing the practical usefulness of any particular definition. Scientific studies on disease definitions or classifications rarely capture the headlines; their results don’t make anyone weak at the knees – yet, they underpin the clinical investigation of all human illnesses and so are immensely important.

The case definitional morass surrounding ME and CFS remains an urgent challenge, and only data, data and more data can bring clarity. Other chronic diseases, such as rheumatoid arthritis and systemic lupus, have previously overcome similar case definition difficulties, so success is certainly possible in an illness like ME/CFS that affects millions throughout the world. It cannot come too soon.

Abstract of report

Title: Study findings challenge the content validity of the Canadian Consensus Criteria for adolescent chronic fatigue syndrome.
Authors: Asprusten TT, Fagermoen E, Sulheim D, Skovlund E, Sørensen Ø, Mollnes TE, Bruun Wyller V, Division of Medicine and Laboratory Sciences, Medical Faculty, University of Oslo, Norway.
Journal: Acta Paediatrica, 2015 Jan 31 (Link).
Aim: The 2003 Canadian Consensus Criteria for chronic fatigue syndrome (CFS) are often assumed to suggest low-grade systemic inflammation, but have never been formally validated. This study explored the content validity of the Criteria in a sample of adolescents with CFS selected according to a wide case definition.
Methods: A total of 120 CFS patients with a mean age of 15.4 years (range 12-18 years) included in the NorCAPITAL project were post hoc subgrouped according to the Canadian Consensus Criteria. Those who satisfied the criteria (Criteria positive) and those who did not (Criteria negative) were compared across a wide range of disease markers and markers of prognosis.
Results: A total of 46 patients were classified as Criteria positive, 69 were classified as Criteria negative and five could not be classified. All disease markers were equal across the two groups, except the digit span backward test of cognitive function, which showed poorer performance in the Criteria positive group. Also, the prognosis over a 30 week period was equal between the groups.
Conclusion: This study questions the content validity of the Canadian Consensus Criteria, as few differences were found between adolescent CFS patients who did and did not satisfy the Criteria.

Further Reading
Myalgic encephalomyelitis/chronic fatigue syndrome: clinical working case definition, diagnostic and treatment protocols [Canadian Consensus Criteria]. Carruthers BM, et al. J Chronic Fatigue Syndr 2003; 11: 7–115 – read an overview (pdf)
What is in a name? Comparing diagnostic criteria for chronic fatigue syndrome with or without fibromyalgia. An ME research UK-funded study – read more
Case definitions for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME): a systematic review. Brurberg KG, et al. BMJ Open 2014; 4: e003973 – read full text
Clinical descriptions of chronic fatigue syndrome. Wikipedia Page – read more