Acute fatigue in chronic fatigue syndrome patients

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) patients often complain that they are more susceptible to acute mental fatigue. It is important to determine whether this is observed using objective tests of sustained attention and responding.

METHODS: Sixty-seven patients who fulfilled the criteria for CFS proposed by Sharpe et al. (1991) were compared with 126 matched healthy controls. Acute fatigue was assessed by comparing performance at the start and end of a lengthy test session and by examining changes over the course of individual tasks.

RESULTS: CFS patients showed impaired performance compared to the controls and these differences increased as the volunteers developed acute fatigue. In addition, differences between the two groups were larger at the end of the test session.

CONCLUSIONS: The present results show that CFS patients are more susceptible to acute fatigue than healthy controls. This could reflect motor fatigue or an inability to compensate for fatigue with increased effort. This profile is consistent with previous research on fatigue and suggests that interpretation of certain aspects of CFS may be helped by considering it as the end point of a continuum of fatigue rather than a distinct disease.

 

Source: Smith AP, Borysiewicz L, Pollock J, Thomas M, Perry K, Llewelyn M. Acute fatigue in chronic fatigue syndrome patients. Psychol Med. 1999 Mar;29(2):283-90. http://www.ncbi.nlm.nih.gov/pubmed/10218920

 

The role of essential fatty acids in chronic fatigue syndrome. A case-controlled study of red-cell membrane essential fatty acids (EFA) and a placebo-controlled treatment study with high dose of EFA

Abstract:

OBJECTIVE: To replicate the treatment study by Behan et al. (1990) using current research criteria for Chronic Fatigue Syndrome (CFS).

METHOD: Fifty patients who fulfilled the Oxford Criteria for CFS were randomly allocated to treatment with either Efamol Marine or placebo for 3 months. They were seen monthly and completed a physical symptoms checklist and the Beck Inventory for Depression and reported if they were the same, better or worse at the end of the study.

RESULTS: Symptoms generally improved with time but not significantly and there were no significant differences between the treatment and placebo groups. Pretreatment red-cell membrane (RBC) lipids of patients compared with age-and sex-matched normal controls showed no significant differences.

DISCUSSION: The results of this study contrast sharply with the previous study where 85% of patients had a clinically significant improvement of symptoms with Efamol Marine over a 3-month treatment period.

 

Source: Warren G, McKendrick M, Peet M. The role of essential fatty acids in chronic fatigue syndrome. A case-controlled study of red-cell membrane essential fatty acids (EFA) and a placebo-controlled treatment study with high dose of EFA. Acta Neurol Scand. 1999 Feb;99(2):112-6. http://www.ncbi.nlm.nih.gov/pubmed/10071170

 

A study of the immunology of the chronic fatigue syndrome: correlation of immunologic parameters to health dysfunction

Abstract:

Surface and intracellular immunologic and apoptotic markers and functional lymphocyte assays after stimulation with anti-CD3/anti-CD28 antibodies or phytohemagglutinin (PHA) were studied in 44 patients fulfilling the Oxford criteria for chronic fatigue syndrome (CFS). Results were then correlated to scores for the Short Form-36 health questionnaire (SF-36), which assesses eight aspects of patient’s well-being, and for the general health questionnaire (GHQ), which detects current psychiatric disorder.

Patients had significantly increased mean fluorescence intensity readings of HLA-DR in CD4 and CD8 cells (P < 0.05). Expression of the costimulatory receptor CD28 in CD8 cells was significantly reduced, and the apoptosis repressor ratio of bcl-2/bax in both CD4 and CD8 was increased in patients (P < 0.05).

Patients with increased HLA-DR expression had significantly lower SF-36 total scores, worse body pains, and poorer general health perception and physical functioning scores. Increased spontaneous lymphocyte proliferation was associated with poor general health perception. PHA proliferative responses were lower in patients with poor emotional and mental health scores, and the anti-CD3/anti-CD28 response was low in those with low general health perception scores.

Higher spontaneous proliferation and reduced PHA responses correlated with higher GHQ scores. Similarly, GHQ scores were significantly higher, indicating worse mental health, in those with lower total SF-36 scores and worse general and mental health scores in the SF-36 questionnaire.

Finally, higher expression of the costimulatory molecule CD28 correlated with higher total SF-36 scores, general health perception and social functioning scores, and with lower role limitation due to physical health. The increased expression of class II antigens and the reduced expression of the costimulatory receptor CD28, which is a marker of terminally differentiated cells, lend further support to the concept of immunoactivation of T-lymphocytes in CFS and may be consistent with the notion of a viral etiopathogenesis in the illness.

We report, for the first time, increased expression of the apoptosis repressor protein bcl-2, which may contribute to enhanced survival of activated lymphocytes. Using the SF-36 health assessment questionnaire and the GHQ, we demonstrated changes in different immunological parameters, each of which correlated with particular aspects of disease symptomatology.

 

Source: Hassan IS, Bannister BA, Akbar A, Weir W, Bofill M. A study of the immunology of the chronic fatigue syndrome: correlation of immunologic parameters to health dysfunction. Clin Immunol Immunopathol. 1998 Apr;87(1):60-7. http://www.ncbi.nlm.nih.gov/pubmed/9576011

 

Graded exercise in chronic fatigue syndrome. Patients were selected group

Comment on: Randomised controlled trial of graded exercise in patients with the chronic fatigue syndrome. [BMJ. 1997]

 

Editor—Kathy Y Fulcher and Peter D White conclude that their findings support the use of graded aerobic exercise in the management of the chronic fatigue syndrome.1 Those readers who delve no further than the abstract and key points may welcome this “take home message.”

Several flaws in the paper, however, make accurate interpretation of the findings difficult and greatly limit its applicability. Firstly, less than two fifths of those screened for the trial actually entered it. Many of those who did not enter it were excluded on the basis of current psychiatric disorder, even though the Oxford criteria used by the authors do not specifically exclude patients with anxiety and depression.2 Given that this is already a subgroup selected by their referral to psychiatric outpatient departments, to select out those with a current psychiatric disorder makes them an unusual group indeed.

Secondly, successful randomisation should make the intervention and control groups similar. Such comparability should enable the problem of confounders, known or unknown, to be accounted for. Evidence of the comparability of cases and controls should be presented.3 Age and sex are almost universal confounders. In this study one might also add body mass index, duration of illness, and even previous athletic training as other possible confounders. The paper does not break down the age and sex of the two groups to enable comparison.

Thirdly, the main outcome measure is the self rated clinical global impression change score. This score is a validated measure of overall change.4 However, the validity of the subsequent categorisation of patients into those with a score of 1 or 2 and those with a score of 3-7, and whether this was a post hoc categorisation, is not stated. A categorisation into 1-3 (all scores representing an improvement) and 4-7 (the rest) would not have produced a significant change. Numerous other physiological outcome measures are provided, but more clinically relevant would have been consultation rates, use of drug treatment, and time off work (time off work was measured only at one year, after the crossover). In short, for those considering the options for managing this condition, especially those who commission services, the message should be that we need more information before we can tell if graded exercise will help most patients with the chronic fatigue syndrome.

You can read the rest of this comment here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2127633/pdf/9361551.pdf

 

Source: Sadler M. Graded exercise in chronic fatigue syndrome. Patients were selected group. BMJ. 1997 Oct 11;315(7113):947-8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2127633/

 

Chronic fatigue syndrome: a qualitative investigation of patients’ beliefs about the illness

Abstract:

The chronic fatigue syndrome is a disabling chronic condition of uncertain cause. Previous studies have found that patients seen in hospital clinics with the syndrome often strongly believe that their illness is physical in nature and minimize the role of psychological and social factors. There is also evidence that patients cope by avoiding activity. However, almost all of these studies have assessed illness beliefs only by questionnaire.

The aim of this study was to explore the nature and origin of illness beliefs in more detail using in-depth interviews and a qualitative analysis of patient responses. Sixty-six consecutive referrals meeting Oxford criteria for chronic fatigue syndrome were recruited. Analysis of responses indicated that, whereas the most commonly described explanation for the illness was a physical one, more than half the patients also believed “stress” had played a role. Patients believed that they could partially control the symptoms by reducing activity but felt helpless to influence the physical disease process and hence the course of the illness.

Patients reported that they had arrived at these beliefs about the illness after prolonged reflection on their own experience combined with the reading of media reports, self help books, and patient group literature. The views of health professionals played a relatively small role. There is potentially a considerable opportunity to help patients arrive at a wider and more enabling explanation of their illness when they first present to primary care.

 

Source: Clements A, Sharpe M, Simkin S, Borrill J, Hawton K. Chronic fatigue syndrome: a qualitative investigation of patients’ beliefs about the illness. J Psychosom Res. 1997 Jun;42(6):615-24. http://www.ncbi.nlm.nih.gov/pubmed/9226609

 

Preliminary determination of a molecular basis of chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS/ME) is a debilitating fatigue illness that has an unknown etiology. We studied 20 chronic fatigue syndrome (CFS) patients, who complied with the Oxford and American CDC definitions, and 45 non-CFS subjects.

Participants completed questionnaires, were clinically examined, and had first morning urine specimens collected, which were screened by gas chromatography-mass spectrometry for changes in metabolite excretion.

Multivariate analysis of the urinary metabolite profiles differed significantly in the CFS patients compared to the non-CFS patients (P < 0.004). The CFS patients had increases in aminohydroxy-N-methylpyrrolidine (P < 0.00003, referred to as chronic fatigue symptom urinary marker 1, or CFSUM1), tyrosine (P < 0.02), beta-alanine (P < 0.02), aconitic acid (P < 0.05), and succinic acid (P < 0.05) and reductions in an unidentified urinary metabolite, CFSUM2 (P < 0.0007), alanine (P < 0.005), and glutamic acid (P < 0.02). CFSUM1, beta-alanine, and CFSUM2 were found by discriminant function analysis to be the first, second, and third most important metabolites, respectively for discriminating between CFS and non-CFS subjects.

The abundances of CFSUM1 and beta-alanine were positively correlated with symptom incidence (P < 0.01 and P < 0.001, respectively), symptom severity, core CFS symptoms, and SCL-90-R somatization (P < 0.00001), suggesting a molecular basis for CFS.

 

Source: McGregor NR, Dunstan RH, Zerbes M, Butt HL, Roberts TK, Klineberg IJ. Preliminary determination of a molecular basis of chronic fatigue syndrome. Biochem Mol Med. 1996 Apr;57(2):73-80. http://www.ncbi.nlm.nih.gov/pubmed/8733884

 

“Abnormal” illness behaviour in chronic fatigue syndrome and multiple sclerosis

Abstract:

OBJECTIVE: To investigate the presence of abnormal illness behaviour in patients with a diagnosis of chronic fatigue syndrome.

DESIGN: A cross sectional descriptive study using the illness behaviour questionnaire to compare illness behaviour scores and illness behaviour profiles of patients with chronic fatigue syndrome and patients with multiple sclerosis.

SETTING: A multidisciplinary fatigue clinic and a teaching hospital neurology outpatient clinic.

SUBJECTS: 98 patients satisfying the Oxford criteria for chronic fatigue syndrome and 78 patients with a diagnosis of multiple sclerosis.

MAIN OUTCOME MEASURE: Responses to the 62 item illness behaviour questionnaire.

RESULTS: 90 (92%) patients in the chronic fatigue syndrome group and 70 (90%) in the multiple sclerosis group completed the illness behaviour questionnaire. Both groups had significantly high scores on the general hypochondriasis and disease conviction subscales and significantly low scores on the psychological versus somatic concern subscale, as measured in relation to normative data. There were, however, no significant differences in the subscale scores between the two groups and the two groups had identical illness behaviour profiles.

CONCLUSION: Scores on the illness behaviour questionnaire cannot be taken as evidence that chronic fatigue syndrome is a variety of abnormal illness behaviour, because the same profile occurs in multiple sclerosis. Neither can they be taken as evidence that chronic fatigue and multiple sclerosis share an aetiology. More needs to be known about the origins of illness beliefs in chronic fatigue syndrome, especially as they are important in determining outcome.

Comment in:

Illness behaviour in the chronic fatigue syndrome and multiple sclerosis. Choice of multiple sclerosis as comparison condition was inappropriate.[BMJ. 1995]

Illness behaviour in the chronic fatigue syndrome and multiple sclerosis. Disentangling common characteristics is not so easy. [BMJ. 1995]

 

Source: Trigwell P, Hatcher S, Johnson M, Stanley P, House A. “Abnormal” illness behaviour in chronic fatigue syndrome and multiple sclerosis. BMJ. 1995 Jul 1;311(6996):15-8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2550080/pdf/bmj00599-0019.pdf (Full article)

 

Chronic fatigue syndrome. Distinguish between syndromes…

Comment in: Chronic fatigue syndrome and myalgic encephalomyelitis. [BMJ. 1994]

Comment on: Longitudinal study of outcome of chronic fatigue syndrome. [BMJ. 1994]

 

EDITOR,-I note that several people writing in the BMY are still confusing myalgic encephalomyelitis with the chronic fatigue syndrome. I wish to clarify matters. From a scientist’s point of view, the main problem is not the term chronic fatigue syndrome but the various diagnostic criteria that go with it. For instance, the strict Australian definition adopted by Wilson et al is similar to that for myalgic encephalomyelitis.2 As a result, it is reasonably certain that in this article the two names probably refer to the same disease.

The “Oxford” criteria used in Britain, however, are far broader, covering all patients whose severe, unexplained fatigue has been present for at least half of the time and for at least six months. The only other requirements are that the fatigue must have had a definite onset and that it affects both physical and mental functioning. Unlike with the strict Australian definition, no immunological criteria have to be met.2 Moreover, there do not have to be appreciable fluctuations in symptoms still a major criterion for myalgic encephalomyelitis.

In terms of prevalence, a recent study found that 17 of 686 (2-5%) attenders in general practice fulfilled the Oxford criteria for the chronic fatigue syndrome.3 When a further four patients who did not meet the criterion of a definite onset were also included the estimated prevalence increased to 3%. In contrast, the prevalence of myalgic encephalomyelitis rarely exceeds 1-5 per 1000.4

Most patients who fulfil the Oxford criteria suffer not from myalgic encephalomyelitis but from more common conditions, notably depression, anxiety states, sleep disorders, and fibromyalgia. None of these disorders occur in epidemics …

You can read the rest of this comment here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2540201/pdf/bmj00440-0053c.pdf

 

Source: Goudsmit EM. Chronic fatigue syndrome. Distinguish between syndromes… BMJ. 1994 May 14;308(6939):1297-8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2540201/

 

The chronic fatigue syndrome

Sir, Although many doctors equate chronic fatigue syndrome (Oxford definition) with what we call myalgic encephalomyelitis (ME), there are some noteworthy differences.

Firstly, in Britain, chronic fatigue syndrome is an umbrella term covering a number of different conditions including neurasthenia, effort syndrome and fibromyalgia. ME is a more specific entity (see the ‘ 10, 1992) and unlike the above, has been closely linked to a persistent infection and immune system activation.

Secondly, while profound fatigue is undeniably the most common symptom of ME, it is rather different from the type of tiredness which people normally experience after exertion. For example, it is often accompanied by feelings of illness which are so unlike anything which people have had before that patients frequently say they cannot describe it. Some have referred to the latter as a severe ‘flu-like’ malaise, others have likened it to being poisoned. Regrettably, having subsumed ME under a general heading of chronic fatigue syndrome, this important and disabling aspect of ME will almost certainly be overlooked.

You can read the rest of this letter here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2399627/pdf/postmedj00050-0083a.pdf

 

Source: Macintyre A, Hume MC. The chronic fatigue syndrome. Postgrad Med J. 1993 Feb;69(808):164. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2399627/

 

Fluctuations in perceived energy and mood among patients with chronic fatigue syndrome

Comment on: Fluctuations in perceived energy and mood among patients with chronic fatigue syndrome. [J R Soc Med. 1992]

 

As one who has long had a high regard for Dr Shepherd’s reasoned arguments in. the area of chronic fatigue syndrome (CFS) (September. 1992 JRSM, p 588), I am sorry to have to point out a logical inconsistency in his assessment of our work. Postinfectious patients do indeed form a sub-group of those with chronic fatigue syndrome. However, according to the ‘Oxford criteria’, in defining other groups of chronically fatigued patients, a diagnosis of previous infection is not necessary. Thus precipitating infection is not necessary for defining the syndrome itself, as we said in our paper.

Secondly, he might do well to note the way in which our results show energy and mood levels among CFS patients to be at their highest in the midmorning. This does not appear to be the pattern typically found among individuals with a primary diagnosis of depression, as we also point out. We regard this distinction as being potentially important and would hope.that the ME Association might wish to consider its implications. Unfortunately, this point was also missed in a recently unsolicited ‘abstraction’ of our work kindly prepared for us by the International Federation of ME Associations to be published in their Medical Update.

You can read the rest of this letter here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1293708/pdf/jrsocmed00106-0076.pdf

 

Source: Wood C. Fluctuations in perceived energy and mood among patients with chronic fatigue syndrome. J R Soc Med. 1992 Oct;85(10):650. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1293708/