ME Research UK — Energising ME Research

ME/CFS: A research and clinical conundrum

Author

Dr Vance Spence, Senior Research Fellow, Vascular Diseases Research Unit, Department of Medicine, University of Dundee, and Chairman of ME Research UK

Presentation

A presentation given on 3rd October 2003 at the workshop ‘New developments in the biology of ME/CFS’ at the West Park Conference Centre, University of Dundee

Part 1

Welcome to everyone attending this research workshop on ME/CFS. As far as we know, this is the first time that the Royal Society of Edinburgh has funded a workshop on the biomedical aspects of this illness. As Dr Kennedy has discussed, the day is divided into two sections, dealing with vascular aspects in the morning and new biochemical developments in the afternoon.

However, my role is to provide an overview of the difficulties surrounding the illness, especially for those of you who are coming fresh to the topic from other scientific areas and specialties. One of our aims is to bring together experts from a variety of disciplines, some with little or no experience of ME/CFS, as we attempt to energise research into this condition with new ideas and novel approaches to solving its inherent problems.

The most widely-used definition of ‘Chronic Fatigue Syndrome’ is that developed in 1994 by a consensus conference: the CDC-1994 definition (1). This was developed in response to criticisms that previous definitions (including the CDC-1988) were too restrictive. It requires the presence of chronic fatigue of six months duration which is persistent or relapsing, of new or definite onset, not substantially alleviated by rest, not the result of ongoing exertion, resulting in a substantial reduction in activities, and leading to substantial functional impairment.

In addition, at least four of the following are required: sore throat, cognitive symptoms, tender lymph nodes, muscle pain, multi-joint pain, headaches, unfreshing sleep and post-exertional malaise. Cognitive or neuropsychiatric symptoms may be present, but the definition excludes clinically important medical conditions such as melancholic depression, substance abuse, bipolar disorder, psychosis and eating disorders. Some would argue that I could just mention this definition and sit down again; but, in fact, it is part of the problem, and it is worth examining why that is so.

As you can see, the definition relies on ‘fatigue’ as its major criterion. For that reason, many patients who fall under this diagnostic label hate the name — they call it the F-word — since, for many of them, ‘fatigue’ per se is not the major problem, and does not best represent how they would explain their condition. Thus, this CDC-1994 definition is now widely recognised to have a number of limitations: symptoms are mainly self-reported (e.g., the clinical signs required in the CDC-1988 definition have been removed); the terminological criteria are vague (e.g., fatigue, malaise, unrefreshing sleep, etc.); the specificity of the definition is poor, allowing heterogeneous groups of patients (e.g., those with somatoform disorders, fibromyalgia syndrome, etc.) to co-exist under the one umbrella term (2, 3); and it makes no attempt to differentiate patients on the basis of severity of illness or level of functional disability.

Indeed, there is a growing realisation that the current CDC-1994-defined ‘CFS’ term is an impossibly inclusive diagnostic construct, begging Simon Loblay (4) to ask the ontological question: “Is CFS a recognisable disease entity with a unique pathophysiology, or is it a ragbag of common non-specific symptoms with many causes, mistakenly labelled as a syndrome?”

As an example, our work in Dundee has compared three groups of patients each fulfilling the CDC-1994 criteria; namely, patients with ME, those with Gulf War Syndrome and patients with a definite history of exposure to organophosphate pesticides. We showed clear differences between the groups in terms of measured parameters, including muscle pain, and physical and mental status (5). Importantly, a high proportion of people in each group had measurable signs of muscle weakness in arms or legs (Figure), indicating that clinical signs can, in fact, be found in these patients if physicians take care to do a full physical examination. Future work will explore such important findings.

Figure 1. Muscle Power in the Legs
Figure. Muscle Power in the Legs

There have been other definitions, apart from the CDC-1994 (Fukuda) one (Table 1). The most recent attempt to revise the definition is based on clinical experiences with very large numbers of patients (6). It will, however, be some time before this new ‘Canadian’ description of ME/CFS replaces the CDC-1994 definition in clinical and research practice.

When comparing scientific studies, it is important to bear in mind that different definitions of ME/CFS may have been used, and this complicates interpretation and comparison of data. It can also be seen from Table 1 below that there have been several attempts in the past decade to define diagnostic criteria for the illness. Each definition has been problematic reflecting, in part, the special interest of the author, and taking little account of the extensive literature, prior to 1988 (Table 1), that made the case for myalgic encephalomyelitis as a distinct clinical entity based on reports of epidemic and endemic cases.

Table 1. Diagnostic criteria (adults) for ‘CFS’-like illness 1988–2003
Diagnostic criteria
‘Canadian’ Expert Consensus Clinical Case Definition for ME/CFS, 2003
US Centers for Disease Control and Prevention, 1994 (1) CFS
World Health Organization, 1994 (non-clinical)
‘Oxford Criteria’ UK, 1991 (7) CFS
Australia, 1990 (8) CFS
London, 1990 (9) ME
US Centers for Disease Control and Prevention, 1988 (10) CFS
Previous literature
Epidemic Neuromyasthenia, 1978 (11)
Myalgic Encephalomyelitis, 1959 (12)
Epidemic Neuromyasthenia, 1959 (13)

References

  1. Fukuda K, Straus S, Hickie I et al and the International Chronic Fatigue Syndrome Study Group. Chronic fatigue syndrome: a comprehensive approach to its definition and study. Ann Intern Med 1994; 121: 953–9.
  2. Salit IE. The chronic fatigue syndrome: a position paper. J Rheumatol 1996; 23: 540–4.
  3. Jason LA, King CP, Richman JA et al. US case definition of Chronic Fatigue Syndrome: diagnostic and theoretical issues. Journal of Chronic Fatigue Syndrome 1999; 5: 3–33.
  4. Loblay RH. Chronic fatigue syndrome: what’s in a name? Med J Aust 1995; 163: 285–6.
  5. Kennedy G et al. The specificity of the CDC-1994 criteria for chronic fatigue syndrome: comparison of health status in three groups of patients who fulfil the criteria. Ann Epidemiol 2004; 14: 95–100.
  6. Carruthers BM, Jain AK, De Meirleir KL et al. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Clinical Working Case Definition, Diagnostic and Treatment Protocols. Journal of Chronic Fatigue Syndrome 2003; 11: 7–115.
  7. Sharpe M, Archard L, Banatvala J et al. Chronic fatigue syndrome: guidelines for research. J R Soc Med 1991; 84: 118–21.
  8. Lloyd AR, Hickie I, Boughton CR et al. Prevalence of chronic fatigue syndrome in an Australian population. Med J Aust 1990; 153: 522–8.
  9. Dowsett EG, Ramsay AM, McCartney RA et al. Myalgic encephalomyelitis — a persistent enteroviral infection? Postgrad Med J 1990; 66: 526–30.
  10. Holmes GP, Kaplan JE, Gantz NM et al. Chronic fatigue syndrome: a working case definition. Ann Intern Med 1988; 108: 387–9.
  11. Parish JG. Early outbreaks of epidemic neuromyasthenia. Postgrad Med J 1978; 54: 711–17.
  12. Acheson ED. The clinical syndrome variously called benign myalgic encephalomyelitis, Iceland disease, and epidemic neuromyasthenia. Am J Med 1959; 26: 569–96.
  13. Henderson DA, Shelokov A. Epidemic Neuromyasthenia — clinical syndrome? N Engl J Med 1959; 260: 757–64.

Link

The Wellcome Trust