Prof. Julia Newton
Institute for Ageing and Health, The Medical School, Newcastle University, Newcastle upon Tyne, UK
Funding for this study has been provided by ME Research UK.
Background and aim
Since 2006, the group at Newcastle University has received several grants from ME Research UK. The largest of these (£130,000), awarded in conjunction with the John Richardson Research Group and the Irish ME Trust in 2007, was to investigate autonomic nervous system parameters along with muscle, liver and heart function in a large patient cohort.
A series of novel scientific papers has emanated from this programme of work, and the researchers have reported that, compared with healthy people, many ME/CFS patients have a) impaired cardiac function, including reduced cardiac mass and blood pool volumes; b) dysfunction of the autonomic nervous system; c) fatigue that is directly related to the burden of autonomic nervous system symptoms; d) an abnormal heart rate response to standing; e) a lower blood pressure, and abnormal blood pressure regulation; and f) substantially slower recovery from standardised exercise of the skeletal muscles (see Scientific progression at the University of Newcastle for links to specific reports).
In the context of ME/CFS, these findings have had an important impact, most particularly in pointing up key areas of importance for diagnosis – a particularly useful outcome given the difficulties of diagnosis faced by patients and clinicians.
At present there are several case definitions for ME/CFS, however (see Clinical Descriptions of Chronic Fatigue Syndrome), but all are exclusionary and rely on collections of non-specific symptoms shared with other illnesses. For example, the most widely-used case definition is the Fukuda (1994) criteria which uses polythetic criteria (i.e., patients are only required to have 4 out of a possible 8 symptoms), but 2 of these 8 symptoms (post-exertional malaise and memory/concentration problems) are thought to be an essential feature of the illness and the Fukuda criteria do not require that these symptoms be present among all patients.
Significant methodological problems could occur if investigators in different settings recruit samples with different percentages of these core symptoms. By contrast, the Canadian clinical case definition (2003) requires specific ME/CFS symptoms such as post-exertional malaise and memory/concentration problems to be present, but this case definition tends to be more complex to apply and has been used relatively rarely for diagnosis or research purposes compared with the more widely used Fukuda definition. Importantly, neither of these definitions has been formally operationalised.
Prof. Leonard Jason at the University of Chicago has been in the forefront of research into the development and application of diagnostic criteria for ME/CFS for more than a decade. In 2010, he developed a standard questionnaire (The DePaul Symptom Questionnaire, DSQ) to assess core symptoms of ME/CFS, with the aim of ensuring that symptoms are assessed in a consistent way across settings to aid in diagnosis.
This questionnaire has now been refined (Jason et al, American Journal of Biochemistry and Biotechnology) and is being made available to other research groups for operational testing on existing ME/CFS cohorts. Importantly, the DSQ now comes in a format which scores symptoms and SF36 data, and produces a “diagnosis” based on several of the more common definitions of ME, CFS and ME/CFS. If this instrument is found to be sufficiently sensitive, it could greatly assist patient diagnosis, saving time (as it can be completed in the patient’s home and brought to the clinic for scoring) and improving confidence in the diagnosis.
In the course of the ME Research UK-funded patient cohort study at Newcastle University, the researchers have collected a large volume of clinical, autonomic and symptom data, and they have available full data sets from almost 200 patients who have attended the Newcastle ME/CFS Service and been referred to their research programme. Each of these patients has been assessed on the basis of the Fukuda 1994 CFS and the Canadian 2003 ME/CFS definitions as part of their clinical examinations, but through the timely development of the DSQ an opportunity has arisen to compare the clinical diagnoses of patients in the Newcastle ME Research UK cohort with those derived from the more structured DSQ instrument.
The results obtained will also be shared with Prof. Jason’s group in Chicago, adding to the data on the usefulness of the DSQ which he hopes to acquire from research groups around the world in different populations of patients. Considering the importance of the ME Research UK cohort and its well-characterised nature, the results could throw valuable light on diagnostic categories and on the utility of the DSQ in practice.