Chronic Fatigue Syndrome: The Current Status and Future Potentials of Emerging Biomarkers

Abstract:

Chronic fatigue syndrome (CFS) remains an incompletely characterized illness, in part due to controversy regarding its definition, biological basis and diagnosis. Biomarkers are objective measures that may lead to improvements in our understanding of CFS by providing a more coherent and consistent approach to study, diagnosis and treatment of the illness. Such metrics may allow us to distinguish between CFS subtypes – each defined by characteristic biomarkers – currently conflated under the single, heterogeneous condition of CFS. These delineations, in turn, may guide more granular, focused, and targeted treatment strategies based on more precise characterizations of the illness. Here, we review potential CFS biomarkers related to neurological and immunological components of the illness, and discuss how these biomarkers may be used to move the field of CFS forward, emphasizing clinical utility and potential routes of future research.

 

Source: Fischer DB, William AH, Strauss AC, Unger ER, Jason L, Marshall GD Jr, Dimitrakoff JD. Chronic Fatigue Syndrome: The Current Status and Future Potentials of Emerging Biomarkers. Fatigue. 2014 Jun 1;2(2):93-109. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4052724/ (Full article)

 

Impaired range of motion of limbs and spine in chronic fatigue syndrome

Abstract:

OBJECTIVE: To determine whether adolescents and young adults with chronic fatigue syndrome (CFS) have a greater prevalence of impaired range of motion (ROM) of the limbs and spine than healthy control patients.

STUDY DESIGN: Case-control study comparing rates of abnormal ROM in 48 consecutive adolescents and young adults with CFS and 48 healthy control patients matched by sex and joint hypermobility. We examined range of ankle dorsiflexion, passive straight-leg raise, seated slump, upper-limb neurodynamic test, prone knee bend, and prone press-up. Abnormal ROM was defined before the study began. The number of abnormal responses ranged from 0 (normal ROM throughout) to 11 (impaired ROM in all areas tested).

RESULTS: The median number of areas with impaired ROM was greater in patients with CFS at the onset of stretch in the involved limb (5 vs 2, P<.001) and at end-range (2 vs 0, P<.001). Patients with CFS were more likely to have greater than 3 areas of impaired ROM (OR 6.0, 95% CI 2.1-17.3; P<.001) and were more likely to develop abnormal symptomatic responses to the individual tests and to the overall assessment (40% vs 4%; P<.001).

CONCLUSIONS: Impaired ROM is more common in subjects with CFS than in healthy adolescents and young adults matched by sex and joint hypermobility. Adding a longitudinal strain to the nerves and soft tissues provoked symptoms in some subjects with CFS. The causes, functional impact, and optimal treatment of these abnormalities warrant further study.

Copyright © 2014 Elsevier Inc. All rights reserved.

 

Source: Rowe PC, Marden CL, Flaherty MA, Jasion SE, Cranston EM, Johns AS, Fan J, Fontaine KR, Violand RL. Impaired range of motion of limbs and spine in chronic fatigue syndrome. J Pediatr. 2014 Aug;165(2):360-6. doi: 10.1016/j.jpeds.2014.04.051. Epub 2014 Jun 11. https://www.ncbi.nlm.nih.gov/pubmed/24929332

 

Adverse events and deterioration reported by participants in the PACE trial of therapies for chronic fatigue syndrome

Abstract:

OBJECTIVE: Adverse events (AEs) are health related events, reported by participants in clinical trials. We describe AEs in the PACE trial of treatments for chronic fatigue syndrome (CFS) and baseline characteristics associated with them.

METHODS: AEs were recorded on three occasions over one year in 641 participants. We compared the numbers and nature of AEs between treatment arms of specialist medical care (SMC) alone, or SMC supplemented by adaptive pacing therapy (APT), cognitive behaviour therapy (CBT) or graded exercise therapy (GET). We examined associations with baseline measures by binary logistic regression analyses, and compared the proportions of participants who deteriorated by clinically important amounts.

RESULTS: Serious adverse events and reactions were infrequent. Non-serious adverse events were common; the median (quartiles) number was 4 (2, 8) per participant, with no significant differences between treatments (P=.47). A greater number of NSAEs were associated with recruitment centre, and baseline physical symptom count, body mass index, and depressive disorder. Physical function deteriorated in 39 (25%) participants after APT, 15 (9%) after CBT, 18 (11%) after GET, and 28 (18%) after SMC (P<.001), with no significant differences in worsening fatigue.

CONCLUSIONS: The numbers of adverse events did not differ significantly between trial treatments, but physical deterioration occurred most often after APT. The reporting of non-serious adverse events may reflect the nature of the illness rather than the effect of treatments. Differences between centres suggest that both standardisation of ascertainment methods and training are important when collecting adverse event data.

Copyright © 2013. Published by Elsevier Inc.

 

Source: Dougall D, Johnson A, Goldsmith K, Sharpe M, Angus B, Chalder T, White P. Adverse events and deterioration reported by participants in the PACE trial of therapies for chronic fatigue syndrome. J Psychosom Res. 2014 Jul;77(1):20-6. doi: 10.1016/j.jpsychores.2014.04.002. Epub 2014 Apr 22. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4065570/ (Full article)

Comment:

Tom Kindlon 2016 Jan 08 3:56 p.m.

“Trial By Error, Continued: Did the PACE Trial Really Prove that Graded Exercise Is Safe?”

By two science journalists: (i) Julie Rehmeyer is a journalist and Ted Scripps Environmental Journalism Fellow at the University of Colorado, Boulder, who has written extensively about ME/CFS and (ii) David Tuller DrPH is academic coordinator of the concurrent masters degree program in public health and journalism at the University of California, Berkeley.

I am quoted in it.

http://www.virology.ws/2016/01/07/trial-by-error-continued-did-the-pace-trial-really-prove-that-graded-exercise-is-safe/

A comparison of health status in patients meeting alternative definitions for chronic fatigue syndrome/myalgic encephalomyelitis

Abstract:

BACKGROUND: Several diagnostic definitions are available for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) that varies significantly in their symptom criteria. This pilot study was conducted to determine whether simple biological and clinical measures differed between CFS/ME patients meeting the 1994 Centres for Disease Control and Prevention (CDC) criteria, the International Consensus Criteria (ICC), as well as healthy controls.

METHODS: A total of 45 CFS/ME patients and 30 healthy controls from the South East Queensland region of Australia provided a blood sample, reported on their current symptoms, as well as aspects of their physical and social health using the Short-Form Health Survey (SF-36), and the World Health Organisation Disability Adjustment Schedule 2.0 (WHO DAS 2.0). Differences were examined using independent sample t-testing.

RESULTS: Patients fulfilling the ICC definition reported significantly lower scores (p < 0.05) for physical functioning, physical role, bodily pain, and social functioning than those that only fulfilled the 1994 CDC definition. ICC patients reported significantly greater (p < 0.05) disability across all domains of the WHO DAS 2.0.

CONCLUSIONS: These preliminary findings suggest that the ICC identifies a distinct subgroup found within patients complying with the 1994 CDC definition, with more severe impairment to their physical and social functioning.

 

Source: Johnston SC, Brenu EW, Hardcastle SL, Huth TK, Staines DR, Marshall-Gradisnik SM. A comparison of health status in patients meeting alternative definitions for chronic fatigue syndrome/myalgic encephalomyelitis. Health Qual Life Outcomes. 2014 Apr 30;12:64. doi: 10.1186/1477-7525-12-64. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4008489/ (Full article)

 

Dimensions of pure chronic fatigue: psychophysical, cognitive and biological correlates in the chronic fatigue syndrome

Abstract:

OBJECTIVES: To investigate associated dimensions of fatigue regarding cognitive impairment, psychomotor performances, muscular effort power and circulating cytokine levels and their relations to symptom intensity in a sample of pure chronic fatigue syndrome (CFS) patients without overlapping objective sleepiness or sleep disorders.

METHODS: 16 CFS patients were compared to 14 matched controls. We assessed structured symptom-scales, polysomnography, multiple sleep latency tests, attention (Zazzo-Cancellation ZCT, digit-symbol-substitution DSST), psychomotor vigilance and speed (PVT, finger tapping test, FTT), dynamometer handgrip force (tonic and phasic trials) and circulating cytokines (IFN-γ, IL-1b, IL-6, IL-8, IL-10, TNF-α).

RESULTS: In addition to fatigue, CFS patients presented with higher affective symptom intensity and worse perceived sleep quality. Polysomnography showed more slow-wave sleep and microarousals in CFS but similar sleep time, efficiency and light-sleep durations than controls. Patients presented with impaired attention (DSST, ZCT), slower reaction times (PVT) but not with lower hit rates (FTT). Notwithstanding lower grip strength during tonic and phasic trials, CFS also presented with higher fatigability during phasic trials. Cytokine levels were increased for IL-1b, IL-8, IL-10 and TNF-α and fatigue intensity was correlated to grip strength and IL-8.

CONCLUSIONS: In contrast to sleepiness, chronic fatigue is a more complex phenomenon that cannot be reduced to one single measured dimension (i.e., sleep propensity). Showing its relations to different measurements, our study reflects this multidimensionality, in a psychosomatic disorder such as CFS. To obtain objective information, routine assessments of fatigue should rule out sleepiness, combine aspects of mental and physical fatigue and focus on fatigability.

 

Source: D, Mairesse O, Montana X, Gilson M, Corazza F, Lefevre N, Linkowski P, Le Bon O, Verbanck P. Dimensions of pure chronic fatigue: psychophysical, cognitive and biological correlates in the chronic fatigue syndrome. Eur J Appl Physiol. 2014 Sep;114(9):1841-51. doi: 10.1007/s00421-014-2910-1. Epub 2014 May 31. https://www.ncbi.nlm.nih.gov/pubmed/24878689

 

Decreased basal ganglia activation in subjects with chronic fatigue syndrome: association with symptoms of fatigue

Abstract:

Reduced basal ganglia function has been associated with fatigue in neurologic disorders, as well as in patients exposed to chronic immune stimulation. Patients with chronic fatigue syndrome (CFS) have been shown to exhibit symptoms suggestive of decreased basal ganglia function including psychomotor slowing, which in turn was correlated with fatigue. In addition, CFS patients have been found to exhibit increased markers of immune activation.

In order to directly test the hypothesis of decreased basal ganglia function in CFS, we used functional magnetic resonance imaging to examine neural activation in the basal ganglia to a reward-processing (monetary gambling) task in a community sample of 59 male and female subjects, including 18 patients diagnosed with CFS according to 1994 CDC criteria and 41 non-fatigued healthy controls. For each subject, the average effect of winning vs. losing during the gambling task in regions of interest (ROI) corresponding to the caudate nucleus, putamen, and globus pallidus was extracted for group comparisons and correlational analyses.

Compared to non-fatigued controls, patients with CFS exhibited significantly decreased activation in the right caudate (p = 0.01) and right globus pallidus (p = 0.02). Decreased activation in the right globus pallidus was significantly correlated with increased mental fatigue (r2 = 0.49, p = 0.001), general fatigue (r2 = 0.34, p = 0.01) and reduced activity (r2 = 0.29, p = 0.02) as measured by the Multidimensional Fatigue Inventory. No such relationships were found in control subjects.

These data suggest that symptoms of fatigue in CFS subjects were associated with reduced responsivity of the basal ganglia, possibly involving the disruption of projections from the globus pallidus to thalamic and cortical networks.

 

Source: Miller AH, Jones JF, Drake DF, Tian H, Unger ER, Pagnoni G. Decreased basal ganglia activation in subjects with chronic fatigue syndrome: association with symptoms of fatigue. PLoS One. 2014 May 23;9(5):e98156. doi: 10.1371/journal.pone.0098156. ECollection 2014. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4032274/ (Full article)

 

A chronic fatigue syndrome model demonstrates mechanical allodynia and muscular hyperalgesia via spinal microglial activation

Abstract:

Patients with chronic fatigue syndrome (CFS) and fibromyalgia syndrome (FMS) display multiple symptoms, such as chronic widespread pain, fatigue, sleep disturbance, and cognitive dysfunction. Abnormal pain sensation may be the most serious of these symptoms; however, its pathophysiology remains unknown.

To provide insights into the molecular basis underlying abnormal pain in CFS and FMS, we used a multiple continuous stress (CS) model in rats, which were housed in a cage with a low level of water (1.5 cm in depth). The von Frey and Randall-Seritto tests were used to evaluate pain levels.

Results showed that mechanical allodynia at plantar skin and mechanical hyperalgesia at the anterior tibialis (i.e., muscle pain) were induced by CS loading. Moreover, no signs of inflammation and injury incidents were observed in both the plantar skin and leg muscles. However, microglial accumulation and activation were observed in L4-L6 dorsal horn of CS rats. Quantification analysis revealed a higher accumulation of microglia in the medial part of Layers I-IV of the dorsal horn. To evaluate an implication of microglia in pain, minocycline was intrathecally administrated (via an osmotic pump). Minocycline significantly attenuated CS-induced mechanical hyperalgesia and allodynia.

These results indicated that activated microglia were involved in the development of abnormal pain in CS animals, suggesting that the pain observed in CFS and FMS patients may be partly caused by a mechanism in which microglial activation is involved.

© 2014 Wiley Periodicals, Inc.

 

Source: Yasui M, Yoshimura T, Takeuchi S, Tokizane K, Tsuda M, Inoue K, Kiyama H. A chronic fatigue syndrome model demonstrates mechanical allodynia and muscular hyperalgesia via spinal microglial activation. Glia. 2014 Sep;62(9):1407-17. doi: 10.1002/glia.22687. Epub 2014 May 23. https://www.ncbi.nlm.nih.gov/pubmed/24852223

 

Neuropsychological impairment in female patients with chronic fatigue syndrome: a preliminary study

Abstract:

This study examines neuropsychological impairments associated with chronic fatigue syndrome (CFS) and explores their association with related clinical factors.

Sixty-eight women with CFS were assessed with a neuropsychological battery. Raw scores were adjusted for age and gender and were converted to T scores according to normative data extracted from a local sample of 250 healthy subjects. Neuropsychological dysfunction was calculated using summary impairment indexes (proportion of test scores outside normal limits-T score <40-for each cognitive domain). Finally, a linear regression was calculated to identify predictors of cognitive deficit, including intrinsic factors of the disease (level of fatigue and length of illness) and extrinsic factors (emotional factors, age, and education).

Approximately 50% of scores showed impairment in attention and motor functioning, and nearly 40% showed impairment in speed information processing and executive functioning. Fatigue predicted attention and executive functioning impairment, and emotional factors predicted verbal memory dysfunction.

According to our findings, cognitive dysfunction in CFS could be explained by pathophysiological processes of the disease. One implication of this would be the need to identify homogeneous subgroups of patients with CFS by taking into account common factors, which, in turn, would help to identify more specific cognitive profiles, which could then serve to implement appropriate therapeutic measures accordingly.

 

Source: Santamarina-Perez P, Eiroa-Orosa FJ, Rodriguez-Urrutia A, Qureshi A, Alegre J. Neuropsychological impairment in female patients with chronic fatigue syndrome: a preliminary study. Appl Neuropsychol Adult. 2014;21(2):120-7. doi: 10.1080/09084282.2013.771264. Epub 2013 Aug 13. https://www.ncbi.nlm.nih.gov/pubmed/24826505

 

Effect of high dose vitamin C on Epstein-Barr viral infection

Abstract:

Background Many natural compounds were tested for the ability to suppress viral replication. The present manuscript details an analysis of high dose vitamin C therapy on patients with EBV infection.

Material and Methods The data were obtained from the patient history database at the Riordan Clinic. Among people in our database who were treated with intravenous vitamin C (7.5 g to 50 g infusions) between 1997 and 2006, 178 patients showed elevated levels of EBV EA IgG (range 25 to 211 AU) and 40 showed elevated levels of EBV VCA IgM (range 25 to 140 AU). Most of these patients had a diagnosis of chronic fatigue syndrome, with the rest being diagnosed as having mononucleosis, fatigue, or EBV infection.

Results Our data provide evidence that high dose intravenous vitamin C therapy has a positive effect on disease duration and reduction of viral antibody levels. Plasma levels of ascorbic acid and vitamin D were correlated with levels of antibodies to EBV. We found an inverse correlation between EBV VCA IgM and vitamin C in plasma in patients with mononucleosis and CFS meaning that patients with high levels of vitamin C tended to have lower levels of antigens in the acute state of disease. In addition, a relation was found between vitamin D levels and EBV EA IgG with lower levels of EBV early antigen IgG for higher levels of vitamin D.

Conclusions The clinical study of ascorbic acid and EBV infection showed the reduction in EBV EA IgG and EBV VCA IgM antibody levels over time during IVC therapy that is consistent with observations from the literature that millimolar levels of ascorbate hinder viral infection and replication in vitro.

 

Source: Mikirova N, Hunninghake R. Effect of high dose vitamin C on Epstein-Barr viral infection. Med Sci Monit. 2014 May 3;20:725-32. doi: 10.12659/MSM.890423. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4015650/ (Full article)

 

Defining recovery in chronic fatigue syndrome: a critical review

Abstract:

PURPOSE: In chronic fatigue syndrome (CFS), the lack of consensus on how recovery should be defined or interpreted has generated controversy and confusion. The purpose of this paper was to systematically review, compare, and evaluate the definitions of recovery reported in the CFS literature and to make recommendations about the scope of recovery assessments.

METHODS: A search was done using the MEDLINE, PubMed, PsycINFO, CINAHL, and Cochrane databases for peer review papers that contained the search terms “chronic fatigue syndrome” and “recovery,” “reversal,” “remission,” and/or “treatment response.”

RESULTS: From the 22 extracted studies, recovery was operationally defined by reference with one or more of these domains: (1) pre-morbid functioning; (2) both fatigue and function; (3) fatigue (or related symptoms) alone; (4) function alone; and/or (5) brief global assessment. Almost all of the studies measuring recovery in CFS did so differently. The brief global assessment was the most common outcome measure used to define recovery. Estimates of recovery ranged from 0 to 66 % in intervention studies and 2.6 to 62 % in naturalistic studies.

CONCLUSIONS: Given that the term “recovery” was often based on limited assessments and less than full restoration of health, other more precise and accurate labels (e.g., clinically significant improvement) may be more appropriate and informative. In keeping with common understandings of the term recovery, we recommend a consistent definition that captures a broad-based return to health with assessments of both fatigue and function as well as the patient’s perceptions of his/her recovery status.

Comment in:

 

Source: Adamowicz JL, Caikauskaite I, Friedberg F. Defining recovery in chronic fatigue syndrome: a critical review. Qual Life Res. 2014 Nov;23(9):2407-16. doi: 10.1007/s11136-014-0705-9. Epub 2014 May 3. https://www.ncbi.nlm.nih.gov/pubmed/24791749

 

Comments

Frank Twisk 2014 Jul 01 11:41 a.m.
A definition of recovery in myalgic encephalomyelitis and chronic fatigue syndrome should be based upon objective measures. Qual Life Res. 2014 Jun 17. doi: 10.1007/s11136-014-0737-1. Twisk FNM.

Abstract

Introduction

Adamowicz and colleagues recently proposed to use “a consistent definition of recovery that captures a broad-based return to health with assessments of both fatigue and function as well as the patients’ perceptions of his/her recovery status” for patients with chronic fatigue syndrome (CFS).

Methods

A qualitative analysis of case definitions for Myalgic encephalomyelitis (ME) and CFS and methods to assess the symptoms and clinical status of ME and CFS patients objectively.

Results

The criteria of CFS define a heterogeneous disorder. ME, often used interchangeably with CFS, is principally defined by muscle weakness, cognitive impairment etc., but above all post-exertional “malaise”: a long-lasting increase in symptoms, e.g. muscle pain and cognitive deficits, after a minor exertion.

The principle symptom of CFS however is “chronic fatigue”. Since post-exertional “malaise” is not obligatory for CFS, only part of the CFS patients meet the diagnostic criteria for ME, while not all ME patients qualify as CFS patients.

There are several accepted methods to assess characteristic symptoms and the clinical status of ME and CFS patients using objective measures, e.g. (repeated) cardiopulmonary exercise tests.

Conclusion

To resolve the debate about the clinical status, proposed effectiveness of therapies and recovery in ME and CFS, it is crucial to accurately diagnose patients using well-defined criteria for ME and CFS and an objective assessment of various typical symptoms, since subjective measures such as “fatigue” will perpetuate the debate.

Comment by Joan Crawford 2014 Jun 04 10:04 a.m. 
Part 2

I’d have liked to have seen this article proposing solid, objective measures be used in the future – ones that have face validity with patients and doctors. Moreover, future trials need to decide if the researchers are aiming at recovery from ill health to as near/close to pre-morbid health (as in like how you’d recover from a severe, debilitating infection) or if they are aim at improving functioning/quality of life as a goal in its own right. This difference ideally should be clearly identified.

The omission of the obvious mathematical/statistical flaws with the use of SF36 PF scale was notable. They miss that using 1SD below mean is not an OK thing to do to compare HC and patients. Doing this is a statistical nonsense. The HC data is massively skewed with a ceiling effect. The bulk of HCs score the max score of 100. (Bowling, 1999, Figure 1). The HC data is not normally distributed so using the mean is not terribly helpful here when comparing and setting standards for recovery. I think using the mode (the value that appears most often in the data sets) would be much more meaningful in this context. Similar will be true of the fatigue scores. There was also no mention of the lowering of the SF36 PF scale outcome measure cut off level in the PACE trial (White et al., 2011). There may well be good reasons for doing so but there was no critical review as to whether the reasons given by White et al were good enough to justify the changes between the proposed pre-trial paper measures (White et al 2007) and the final Lancet one. I notice that White was a co-author of the Knoop (2007) paper that selected a SF36 PF score of -1SD as recovered but in a later trial (White et al., 2011) this was reduced to 60 (-2SD). This is quite a leap by the same investigator.

I particularly do not like their pathologisation/speculation of the role of pre-morbid patient functioning. Action prone nonsense. No one can or are they ever likely to prove objectively that pwME/CFS were overactive/overambitious/action prone before getting ill. I hear people mourning the loss of activities, relationships and careers they cherished and enjoyed immensely. So now they cannot even talk about their pre-illness time without feeling psychologised? To not take a more critical view of this is a real let down for me. It’s subjective, speculative nonsense that is unprovable. Patients have a right to get annoyed when they are psychologised in this manner. It should be rather obvious that patients have ex-work colleagues and friends who worked as hard (or harder, longer, faster) than them who are still employed, with families, fit and well with fulfilling lives. PwME/CFS cannot do this because they are sick. Not because they overdid it a bit. That is burnout, not ME/CFS. I thought it remiss to not see the other side regarding how the impact of this speculation might affect patients. Moreover, there are plenty of not especially ambitious, couch potatoes who are ill!

How recovery in ME/CFS is operationalised in the future requires more critical thought and this must take into account how the patients define recovery and must be able to be demonstrated objectively (Haywood et al., 2011).

References:

Anthony, W. A. (1993) Recovery from mental illness: the guiding vision of the mental health service system in the 1990s. Psychosocial Rehabilitation Journal, 16, 11-23.

Bowling A., Bond, M., Jenkinson, C., & Lamping, D.L. (1999). Short Form 36 (SF-36) Health Survey questionnaire: which normative data should be used? Comparisons between the norms provided by the Omnibus Survey in Britain, the Health Survey for England and the Oxford Healthy Life Survey. Journal of Public Health Medicine. 21(3):255-70.

Haywood, K.L., Staniszewska, S., & Chapman, S. (2011). Quality and acceptability of patient-reported outcome measures used in chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME): A systematic review. Quality of Life Research, In press.

Knoop, H., Bleijenberg, G., Gielissen, M. F. M., van der Meer, J.W. M., & White, P. D. (2007). Is a full recovery possible after cognitive behavioral therapy for chronic fatigue syndrome? Psychotherapy and Psychosomatics, 76, 171–176.

Lester, H., & Gask, L. (2006). Delivering medical care for patients with serious mental illness or promoting a collaborative model of recovery. British Journal of Psychiatry, 188, 401–402.

White, P.D., Sharpe, M.C., Chalder, T., DeCesare, J.C., Walwyn, R; on behalf of the PACE trial group. (2007). Protocol for the PACE trial: a randomised controlled trial of adaptive pacing, cognitive behaviour therapy, and graded exercise, as supplements to standardised specialist medical care versus standardised specialist medical care alone for patients with the chronic fatigue syndrome/myalgic encephalomyelitis or encephalopathy. BioMed Cent Neurology, 7:6.

White, P.D., Goldsmith, K.A., Johnson, A.L., Potts, L., Walwyn, R., DeCesare, J.C., et al. (2011). Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): A randomised trial. Lancet, 5, 377(9768), 823-836.
Comment by Joan Crawford 2014 Jun 04 10:01 a.m.edited 
Part 1

This paper has a great description of the differences between ‘recovery’ versus ‘adaptation/feeling better’. As a patient I describe this as the difference between ‘feeling better’ and ‘being better’ (i.e. recovered to point comparable with pre-existing health given age increase with ability to return to work/social life without the presence of limiting symptoms). These things appear to get muddled in many clinical trials. I suspect anyone feeling poorly will feel a bit or a lot better after a psychological intervention with a concerned, empathic individual, however, whether this has any impact on their underlying condition or activity levels needs to be shown by objective measures.

It was a disappointment that in this paper there was no push for more objective measures of patient functioning to be used in future research work. For example, pedometers, actigraphy, neuropsychological tests, 2 day exercise testing (if well enough at baseline), using simple dynamometers taking readings over 2 days, return to work/school (or ability to do if the person wished), move from incapacity/sickness welfare payments to job seeking benefits and so on. I’m perplexed when researchers claim that patients are recovered if they continue to receive incapacity/ill health payments. Perhaps in this condition it might be worth measuring whether saliva cortisol levels and NK cell functioning normalise. At a push even the simple 6 minute walking test could be helpful. Objective measures need not be expensive. Simple, reliable and cheap equipment such as pedometers are available for around $30 and can show really well if a patient who is doing better over time. This could be used quite simply to get around the issue of is the patient feeling better because they are actually doing less that is discussed in the review. It’s a shame that straightforward solutions like this were not suggested.

Within the paper the authors refer to Lester & Gask (2006), which includes a popular definition of recovery from within mental health context by William Anthony as: “‘a way of living a satisfying, hopeful and contributing life even with the limitations caused by illness. Recovery involves the development of a new meaning and purpose in one’s life as one grows beyond the catastrophic effects of mental illness’ (Antony, 1993: p. 21). I had not seen this definition before for recovery so it was educating to be made aware that this was a widely used concept. To me that defines adaptation, not recovery. I would not be happy with researchers who decided that that was a good place to start defining recovery from ME/CFS. I’d want the goal to be at a minimum to not feel ill or sick or debilitated and able to be free of disease symptoms and normal functioning for the patient for their age.

References and Part 2 above