critique – Page 2 – American ME and CFS Society

A review of the definitional criteria for chronic fatigue syndrome

Abstract:

RATIONALE, AIMS AND OBJECTIVES: The research community has for more than three decades tried to unravel the diagnostic mystery that is Chronic Fatigue Syndrome (CFS). This has resulted in considerable amounts of time and money being invested in attempts aimed at establishing the aetiology and pathogenesis of CFS. All of this investment has produced evidence of an interesting variety of endocrine, immune, infectious, muscular and neurological abnormalities in CFS; however, the cause remains elusive. The absence of a known causative agent or diagnostic test for CFS has resulted in the development of a number of CFS case definitions. As such, the main objectives of this paper are to provide a critical review of the similarities and differences between the varying approaches to CFS case definition. The conflicts and controversies that have emerged as a result of the differing definitional criterion for CFS are highlighted and the potential impact on future research is identified.

METHODS, RESULTS AND CONCLUSIONS: This paper presents a critical review of the most frequently used case definitions in CFS. There are currently five case definitions of CFS; however, the most prominent and widely used of these definitions is the 1994 Centre for Disease Control and Prevention Case Definitions. However, the pre-eminence of this definition over the others has never been substantiated and it has been widely criticized for its lack of specificity. Furthermore, none of the above case definitions have produced evidence to demonstrate their accuracy or precision at defining cases of CFS. A summary description of the symptom profile included in each of the case definitions is provided. The inconsistencies that have emerged in CFS research as a consequence of differing approaches to case definition are also highlighted and discussed.

Source: Christley Y, Duffy T, Martin CR. A review of the definitional criteria for chronic fatigue syndrome. J Eval Clin Pract. 2012 Feb;18(1):25-31. doi: 10.1111/j.1365-2753.2010.01512.x. Epub 2010 Oct 4. https://www.ncbi.nlm.nih.gov/pubmed/21029269

Chronic fatigue syndrome: Harvey and Wessely’s (bio)psychosocial model versus a bio(psychosocial) model based on inflammatory and oxidative and nitrosative stress pathways

Abstract:

BACKGROUND: In a recently published paper, Harvey and Wessely put forward a ‘biopsychosocial’ explanatory model for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), which is proposed to be applicable to (chronic) fatigue even when apparent medical causes are present.

METHODS: Here, we review the model proposed by Harvey and Wessely, which is the rationale for behaviourally oriented interventions, such as cognitive behaviour therapy (CBT) and graded exercise therapy (GET), and compare this model with a biological model, in which inflammatory, immune, oxidative and nitrosative (IO&NS) pathways are key elements.

DISCUSSION: Although human and animal studies have established that the pathophysiology of ME/CFS includes IO&NS pathways, these abnormalities are not included in the model proposed by Harvey and Wessely. Activation of IO&NS pathways is known to induce fatigue and somatic (F&S) symptoms and can be induced or maintained by viral and bacterial infections, physical and psychosocial stressors, or organic disorders such as (auto)immune disorders. Studies have shown that ME/CFS and major depression are both clinical manifestations of shared IO&NS pathways, and that both disorders can be discriminated by specific symptoms and unshared or differentiating pathways. Interventions with CBT/GET are potentially harmful for many patients with ME/CFS, since the underlying pathophysiological abnormalities may be intensified by physical stressors.

CONCLUSIONS: In contrast to Harvey and Wessely’s (bio)psychosocial model for ME/CFS a bio(psychosocial) model based upon IO&NS abnormalities is likely more appropriate to this complex disorder. In clinical practice, we suggest physicians should also explore the IO&NS pathophysiology by applying laboratory tests that examine the pathways involved.

Source: Maes M, Twisk FN. Chronic fatigue syndrome: Harvey and Wessely’s (bio)psychosocial model versus a bio(psychosocial) model based on inflammatory and oxidative and nitrosative stress pathways. BMC Med. 2010 Jun 15;8:35. doi: 10.1186/1741-7015-8-35. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2901228/ (Full article)

Graded exercise for chronic fatigue syndrome: too soon to dismiss reports of adverse reactions

Sir,

Given there is no formal system to report adverse reactions to non-pharmacological interventions such as graded exercise therapy (GET) for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME), other sources of data need to be considered when evaluating safety. As noted by Clark & White, a large survey conducted in 2001 by the charity Action for ME found that 50% of patients who received graded exercise felt worse (1, 2). They also referred to a subsequent study by the same group suggesting that many patients might not have been treated by experienced therapists (3). However, the sample was small and, as in all surveys, therapist competence was not assessed.

A review of all the surveys conducted to date not only supports the view that a significant proportion of patients experience adverse reactions following GET, but also that it is premature to attribute those reactions to practitioner inexperience or inadequate training (1, 4). For example, the results of a recent survey conducted by the ME Association showed that of the 906 individuals who had received GET, 33.1% felt “much worse” and 23.4% judged themselves to be “slightly worse” (4). Similarly, a survey of patients who had been treated in the previous 3 years, i.e. following the refinement of the protocol as discussed by Clark & White, revealed that 34% of the 722 who had tried GET perceived themselves to be worse (5).

Without details of the training of the therapist and their fidelity to the treatment manual, one can only speculate about the factors associated with poor outcome. Nijs et al. (6) discussed some of the possible reasons. However, there are additional factors that deserve consideration when evaluating the efficacy and safety of GET. Firstly, the survey results may reflect, at least in part, the experiences of patients receiving treatment in a clinical setting. As has been shown in studies on other interventions, the outcomes documented in routine practice may be more realistic than those obtained in randomized controlled trials (7). Secondly, many patients may not be able to complete graded activity schedules for various reasons, including ongoing pathology. For instance, Black & McCully (8) used an accelerometer to measure activity levels before, during and after a 4-week “training period” consistent with GET. They documented an increase in activity counts lasting between 4 and 10 days, and this was associated with higher scores for pain and fatigue. The inability to sustain target activity levels was also noted by Friedberg (9), who followed the progress of one patient during 26 sessions of GET. He recorded a 10.6% decrease in mean weekly step counts, leading Friedberg to speculate that the subjective measures of improvement might have been the result of activity substitution and a corresponding reduction in perceived stress.

Finally, we were surprised that neither of the letters cited the research by White et al. (10). This elegant study supports the growing evidence of abnormal metabolic and immunological reactions to exercise in subsets with CFS. Although their sample was small, White et al. found elevated concentrations of the pro-inflammatory cytokine tumour necrosis factor-alpha at time-points of 3 h and 3 days after exercise. In addition, they documented increased levels of the anti-inflammatory cytokine transforming growth factor-beta after normal exertion. We therefore concur with Nijs et al. (6) as well as other researchers, that GET may not be appropriate for all patients with CFS and that pacing may provide a useful, acceptable and safe alternative (6, 11, 12).

You can read the rest of this letter here: https://www.medicaljournals.se/jrm/content/abstract/10.2340/16501977-0493

Comment on: Chronic fatigue syndrome. [J Rehabil Med. 2008]

Source: Kindlon T, Goudsmit EM. Graded exercise for chronic fatigue syndrome: too soon to dismiss reports of adverse reactions. J Rehabil Med. 2010 Feb;42(2):184; author reply 184-6. doi: 10.2340/16501977-0493. https://www.medicaljournals.se/jrm/content/abstract/10.2340/16501977-0493 (Full article)

A review on cognitive behavorial therapy (CBT) and graded exercise therapy (GET) in myalgic encephalomyelitis (ME) / chronic fatigue syndrome (CFS): CBT/GET is not only ineffective and not evidence-based, but also potentially harmful for many patients with ME/CFS

Abstract:

Benign Myalgic Encephalomyelitis (ME) / Chronic Fatigue Syndrome (CFS) is a debilitating disease which, despite numerous biological abnormalities has remained highly controversial. Notwithstanding the medical pathogenesis of ME/CFS, the (bio)psychosocial model is adopted by many governmental organizations and medical professionals to legitimize the combination of Cognitive Behavioral Therapy (CBT) and Graded Exercise Therapy (GET) for ME/CFS. Justified by this model CBT and GET aim at eliminating presumed psychogenic and socially induced maintaining factors and reversing deconditioning, respectively.

In this review we invalidate the (bio)psychosocial model for ME/CFS and demonstrate that the success claim for CBT/GET to treat ME/CFS is unjust. CBT/GET is not only hardly more effective than non-interventions or standard medical care, but many patients report that the therapy had affected them adversely, the majority of them even reporting substantial deterioration.

Moreover, this review shows that exertion and thus GET most likely have a negative impact on many ME/CFS patients. Exertion induces post-exertional malaise with a decreased physical performance/aerobic capacity, increased muscoskeletal pain, neurocognitive impairment, “fatigue”, and weakness, and a long lasting “recovery” time.

This can be explained by findings that exertion may amplify pre-existing pathophysiological abnormalities underpinning ME/CFS, such as inflammation, immune dysfunction, oxidative and nitrosative stress, channelopathy, defective stress response mechanisms and a hypoactive hypothalamic-pituitary-adrenal axis.

We conclude that it is unethical to treat patients with ME/CFS with ineffective, non-evidence-based and potentially harmful “rehabilitation therapies”, such as CBT/GET.

Source: Twisk FN, Maes M. A review on cognitive behavorial therapy (CBT) and graded exercise therapy (GET) in myalgic encephalomyelitis (ME) / chronic fatigue syndrome (CFS): CBT/GET is not only ineffective and not evidence-based, but also potentially harmful for many patients with ME/CFS. Neuro Endocrinol Lett. 2009;30(3):284-99. https://www.ncbi.nlm.nih.gov/pubmed/19855350

Response to: exercise performance and chronic pain in chronic fatigue syndrome: the role of pain catastrophizing

Nijs and colleagues [1] have found various correlations; however, they have not proven the direction of causation or shown what can be done with the information. As is well known, pain can have a protective effect; conditions involving a lack of sensitivity to pain can cause all sorts of extra complications. Knowledge of why patients with chronic fatigue syndrome (CFS) experience pain following exercise is far from complete. However, studies in recent years such as by Jammes [2] and Sorensen [3] give possible clues that something abnormal biochemically occurs.

The authors found no association between either the current employment rate or the percentage difference between premorbid and current employment rate and either the Pain Catastrophizing Scale, the Beck Depression Inventory score or the SF-36 bodily pain score so none of these can explain the large drop in the employment rate found in the patients in this study and in other studies, suggesting the involvement of an independent variable. The single exercise test methodology used may not find the disease-specific factors associated with the exercise intolerance in CFS; repeat exercise testing such as 24 hours apart “may be necessary to document the atypical recovery response and protracted malaise unique to CFS”[4]. In the world of employment, most jobs do not involve just one intense burst of activity; continuous work, more comparable with repeat exercise testing, is generally required to hold on to a job.

The authors refer to CFS patients supposedly having “personality traits” “involving activity-avoidance.” However studies such as Harvey et al. [5] suggest CFS patients were more active than their contemporaries pre-illness suggesting that if patients avoid activity, it is unlikely to be due to “personality traits.”

You can read the rest of this comment here: http://painmedicine.oxfordjournals.org/content/10/6/1144.long

Comment on: Exercise performance and chronic pain in chronic fatigue syndrome: the role of pain catastrophizing. [Pain Med. 2008]

Source: Kindlon T. Response to: exercise performance and chronic pain in chronic fatigue syndrome: the role of pain catastrophizing. Pain Med. 2009 Sep;10(6):1144; author reply 1145-6. doi: 10.1111/j.1526-4637.2009.00690.x. Epub 2009 Sep 9. http://painmedicine.oxfordjournals.org/content/10/6/1144.long (Full article)

Change in grey matter volume cannot be assumed to be due to cognitive behavioural therapy

Comment on: Can CBT substantially change grey matter volume in chronic fatigue syndrome? [Brain. 2009]

Sir, In their reply to Dr Bramsen, De Lange et al. (2008) use a type of circular reasoning: cognitive behavioural therapy (CBT), they say, has previously been shown to be ‘effective’ for chronic fatigue syndrome (CFS) so the change they measured must be due to CBT.

First, it needs to be pointed out that CBT is far from a panacea for CFS. A recent meta-analysis (Malouff et al., 2008) of the efficacy of CBT in treating CFS found an effect size of d = 0.48 (95% CI 0.27–0.69).

In their letter, De Lange et al. (2008) refer to a review by Whiting et al. (2001) as part-evidence for their claim that CBT is effective for CFS. However, this review recommended the use of objective outcome measures e.g.

Outcomes such as ‘improvement,’ in which participants were asked to rate themselves as better or worse than they were before the intervention began, were frequently reported. However, the person may feel better able to cope with daily activities because they have reduced their expectations of what they should achieve, rather than because they have made any recovery as a result of the intervention. A more objective measure of the effect of any intervention would be whether participants have increased their working hours, returned to work or school, or increased their physical activities’.

Given one of the aims of CBT (for CFS) has been said to be ‘increased confidence in exercise and physical activity’ (O’Dowd et al.), we cannot have complete confidence that the improvements recorded in CBT trials thus far represent objective improvements [such as improvements in grey matter volume (GMV)], rather than simply being due to altering how patients answer questionnaires. An INAMI report (2006) on the use of CBT (combined with GET) in over 600 CFS patients in Belgium found that while patients reported improvements on their fatigue scores, there was negligible change on the tests of exercise capacity and there was actually a worsening of their employment status (as measured by the amount of hours worked per week), both at the end of the intervention and at follow-up.

You can read the rest of this comment here: http://brain.oxfordjournals.org/content/132/7/e119.long

Source: Kindlon T. Change in grey matter volume cannot be assumed to be due to cognitive behavioural therapy. Brain. 2009 Jul;132(Pt 7):e119; author reply e120. doi: 10.1093/brain/awn358. Epub 2009 Jan 29. http://brain.oxfordjournals.org/content/132/7/e119.long (Full article)

Can CBT substantially change grey matter volume in chronic fatigue syndrome?

Sir, I wish to comment on the paper ‘Increase in prefrontal cortical volume following cognitive behavioural therapy (CBT) in patients with chronic fatigue syndrome (CFS)’ (De Lange et al., 2008). The authors compared the grey matter volume (GMV) of 22 patients with CFS before and after treatment with CBT, and with 22 healthy controls who were assessed at a similar time interval but received no treatment. The patient sample at baseline had a 5% smaller GMV as compared to healthy controls. In patients, GMV at baseline was correlated with slow information processing speed and physical activity. At follow-up, in the patient group, mean GMV increased with 0.7% from 669.4 to 674.1 ml. This increase in GMV was correlated with changes in cognitive speed. On the basis of this result, the authors conclude ‘that the cerebral atrophy associated with CFS is partially reversed after effective CBT’. In the Netherlands, a press release of the author’s institution even states ‘CBT brings about structural changes in brains of patients’ (Radboud University, 2008). The question arises whether the study results indeed support such far reaching conclusions.

Two critical points need to be taken into consideration. First, the authors did not include a control group of patients receiving no treatment or a different treatment. Therefore, the increase in GMV cannot be attributed to the CBT treatment given. It is possible that the natural course of and fluctuations in the illness are responsible for this result. In addition, it might be possible that other treatments than CBT would have resulted in the same, or even better, results. Second, even if the results were indeed to be attributed to changes in lifestyle brought about by CBT, several questions still remain. To name a few, first, the increase in volume of <1% is very modest. Therefore, the question is whether, although statistically significant, this small increase is also of clinical significance. Second, if CBT brings about changes in lifestyle, and these changes are responsible for small improvements in the patients’ brain and activity levels, are these changes structural and related to the primary disease process? An alternative interpretation is that changing the lifestyle of patients, influences their quality of life, activity patterns and GMV, while the underlying disease process is not influenced.

Another critical remark relates to the fact that the authors in their paper do not mention the proportion of absolute increase in GMV of 0.7%, but rather report that the initial between-group difference between patients and healthy controls decreases with 12%. For readers, it is important to realize that the measure of change reported by the authors is influenced by the absolute size of the between-group difference: the smaller, and therefore less relevant, this difference is, the larger the reported proportion becomes, thereby making less relevant results looking more impressive.

The above considerations lead to the conclusion, that the author’s results, although interesting, do not support the far reaching conclusions regarding the power of CBT.

You can read the rest of this comment here: http://brain.oxfordjournals.org/content/132/6/e110.long

Comment in: Change in grey matter volume cannot be assumed to be due to cognitive behavioural therapy. [Brain. 2009]

Comment on: Increase in prefrontal cortical volume following cognitive behavioural therapy in patients with chronic fatigue syndrome. [Brain. 2008]

Source: Bramsen I. Can CBT substantially change grey matter volume in chronic fatigue syndrome? Brain. 2009 Jun;132(Pt 6):e110; author reply e111. doi: 10.1093/brain/awn207. Epub 2008 Aug 29. http://brain.oxfordjournals.org/content/132/6/e110.long (Full article)

NICE behaviour: ME guideline is unworkable

Comment on: Diagnosis and management of chronic fatigue syndrome or myalgic encephalomyelitis (or encephalopathy): summary of NICE guidance. [BMJ. 2007]

The National Institute for Health and Clinical Excellence (NICE) recommends that everyone with mild or moderate myalgic encephalopathy/chronic fatigue syndrome (ME/CFS) should be offered a course of either cognitive behaviour therapy (CBT) or graded exercise therapy (GET).1

This is despite published evidence remaining weak (especially for group CBT) and inconsistent 2. Patient evidence submitted to the chief medical officer’s report concluded that CBT produced “no change” in 67% of cases and made the condition “worse” in 26% of cases.3 Around 50% of respondents reported that inappropriate exercise therapy had also made their condition “worse.”3

When the NICE estimate on prevalence is used this controversial recommendation will affect some 200 000 people. A one to one course of CBT covering 12 to 16 sessions will cost well over £1500. The cost of a professionally supervised exercise therapy programme is also likely to be substantial.

So where is around £300 million of new money going to come from at a time when very limited funding for some of the newly established NHS clinical services for people with ME/CFS is now being cut?4 And where are all the therapists going to come from? Those already in post often cannot even cope with their current workload.

These are important questions that I raised at a NICE implementation and planning meeting in October 2006—but nobody from NICE could provide a convincing answer. These recommendations are going to be of no value whatsoever to many people with ME/CFS. They are also going to be impossible to implement owing to a lack of both funding and human resources.

You can read the rest of this comment here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1976494/

Source: Shepherd CB. NICE behaviour: ME guideline is unworkable. BMJ. 2007 Sep 15;335(7619):528. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1976494/ (Full article)

How common is chronic fatigue syndrome; how long is a piece of string?

Comment on: Prevalence of chronic fatigue syndrome in metropolitan, urban, and rural Georgia. [Popul Health Metr. 2007]

One of the most difficult tasks in medicine is to accurately measure how common illnesses are. Why do we do it? Justifications include being able to plan health care and public health priorities, as well as highlighting specific diseases for extra funding for both health care and research. Yet the jobbing physician at the sharp edge of clinical practice cares little about the exact prevalence of a disease or illness, since this is all too obvious from the frequency of the problems presented by patients who come through the door.

You can read the rest of this comment here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1904177/

Source: White PD. How common is chronic fatigue syndrome; how long is a piece of string? Popul Health Metr. 2007 Jun 8;5:6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1904177/ (Full article)

Chronic fatigue syndrome

I have just read the review of treatments for chronic fatigue syndrome (CFS) in the October issue of the JRSM. It included my study, but some of the details were inaccurate and the overall judgement was unfair and potentially misleading.

In the original ‘York’ review of the various treatments for CFS, my study received a validity score of two. However, after clarification regarding the statistical analysis, this was changed to three (Kleijnen, personal communication). Chambers et al. were clearly not aware of the ‘correction’ and published the original score. It’s a minor issue, but it wasn’t the only one.

Another example relates to the assessment of the results. According to the table (p. 511), the programme had no overall effect—but as the authors noted in their recent review for NICE (http://www.nice.org.uk/page.aspx?o=368933, appendix 1, p. 423), there were ‘significant differences between groups for fatigue… and somatic symptoms’. They would also have been aware that 82% of the patients rated themselves as ‘better’ or ‘much better’ and that 23% had improved to such a degree that they were discharged.

To summarize, patients reported less fatigue, fewer somatic symptoms, less anxiety and depression after six months compared to the controls, and the improvements were maintained at follow-up. Yet the authors judged the treatment had ‘no overall effect’.

My study is one of the few which has assessed an alternative to the CBT-based programmes. It’s also one of the few controlled trials to include pacing, a strategy which many patients regard as a particularly helpful way of managing their limited energy. In my opinion, it deserved an accurate evaluation and a fair summary of the outcome. It didn’t get that.

You can read the rest of this comment here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1761664/

Comment on: Interventions for the treatment, management and rehabilitation of patients with chronic fatigue syndrome/myalgic encephalomyelitis: an updated systematic review. [J R Soc Med. 2006]

Source: Goudsmit EM. Chronic fatigue syndrome. J R Soc Med. 2007 Jan;100(1):7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1761664/ (Full article)