Number 2 |
1st June 2008 |
Nater, UM., Youngblood, LS., Jones, JF., Unger, ER., Miller, AH., Reeves, WC and Heim, C.ENDOCRINOLOGY AND NEUROENDOCRINOLOGY
The objective was to examine diurnal salivary cortisol rhythms and plasma IL-6 concentrations in persons with CFS (CDC criteria ’94), persons not fulfilling a diagnosis of CFS (ISF) and nonfatigued controls (NF). Previous studies of CFS patients have implicated the hypothalamic-pituitary-adrenal (HPA) axis and the immune system in the pathophysiology of CFS, although results have been equivocal.
Twenty-eight people with CFS, 35 persons with ISF, and 39 NF identified from the general population of Wichita, Kansas, were admitted to a research ward for 2 days. Saliva was collected immediately on awakening (6:30 AM), at 08:00 AM, 12 noon, 4:00 PM, 8:00 PM and at bedtime (10:00 PM) and plasma was obtained at 7:30 AM. Salivary cortisol concentrations were assessed using radioimmunoassay, and plasma IL-6 was measured using sandwich enzyme-linked immunosorbent assay.
People with CFS demonstrated lower salivary cortisol concentrations in the morning and higher salivary cortisol concentrations in the evening compared with both ISF and NF groups indicating a flattening of the diurnal cortisol profile. Mean plasma IL-6 concentrations were highest in CFS compared with the other groups, although these differences were no longer significant after controlling for BMI. Attenuated decline of salivary cortisol concentrations across the day and IL-6 concentration were associated with fatigue symptoms in CFS.
These results suggest an altered diurnal cortisol rhythm and IL-6 concentrations in CFS cases identified from a population-based sample.
Hokama, Y., Empey-Campora, C., Hara, C., Higa, N., Siu, N., Lau, R., Kuribayashi, T and Yabusaki, K. Acute phase phospholipids related to the cardiolipin of mitochondria in the sera of patients with chronic fatigue syndrome (CFS), chronic ciguatera fish poisoning (CCFP), and other diseases attributed to chemicals, Gulf War, and marine toxin. Journal of Clinical Laboratory Analysis, 2008, 22, 2, 99-105.
This study examined sera from 328 patients with CFS (CDC criteria ’94) with sera from 17 people with CCFP, 8 Gulf War Veterans (GWV), 24 men with Prostate Cancer (PC), and 52 normal sera in the modified Membrane Immunobead Assay (MIA) procedure for CTX. The CFS patients' sera were examined by the modified MIA with purified MAb-CTX and 91.2% gave a titre >1:40. 76% of the 17 CCFP sera samples and 100% of the 8 GWV sera samples also had a titre >1:40. 92.3% of 52 normal sera showed titres of 1:20 or less, while 4 gave titres of >1:40. In addition, 41 sera were examined for Anti-Cardiolipin (aCL) by a commercial ELISA procedure with 87.8% demonstrating IgM, IgM+IgA, or IgM+IgG aCL antibodies. These results showed mostly the IgM aCL antibody alone in the sera samples. In addition, 41 serum samples were examined for aCL, with 37 showing positive for aCL, representing 90.2% positive for the three disease categories examined: CFS, CCFP and GWV.
Examination for antiMitochondrial-M2 autoantibody (aM-M2) in 28 patients [CFS (18), CCFP (5), and GWV (5)] was negative for aM-M2. Inhibition analysis with antigens, ciguatoxin (CTX – a marine toxin), CFS "Acute Phase Lipids", commercial Cardiolipin (CL) and 1,2-Dipalmitoyl-sn-Glycero-3-[Phospho-L-Serine] (PS) and antibodies, MAb-CTX and aCL from patients' serum show that the phospholipids in CL and CTX are antigenically indistinguishable with antibodies MAb-CTX and CFS-aCL. Preliminary chemical analyses have shown the lipids to be phospholipids associated with CL of the mitochondria. We designate this "Acute Phase Lipid" comparable to "Acute Phase Proteins" [C-reactive protein (CRP) and Serum Amyloid A (SAA)] in inflammatory conditions.
It is suggested that the increase in phospholipids is associated with CL and all may be associated with defective mitochondrial metabolism and thus apoptosis in regulation of program cell death... hence the immune dysfunction status in CFS disease.
[Ed. Note: MAb refers to monoclonal antibodies.]
Naschitz, JE., Slobodin, G., Sharif, D., Fields, M., Isseroff, H., Sabo, E and Rosner, I. Electrocardiographic QT interval and cardiovascular reactivity in fibromyalgia differ from chronic fatigue syndrome. European Journal of Internal Medicine, 2008, 19, 3, 187-191.
Fibromyalgia (FM) and CFS frequently overlap clinically and have been considered variants of one common disorder. We have recently shown that CFS is associated with a short corrected electrocardiographic QT interval (QTc). In the present study, we evaluated whether FM and CFS can be distinguished by QTc.
The study groups were comprised of women with FM (n=30) and with CFS (CDC criteria ’94, n=28). The patients were evaluated with a 10 minute supine-30 minute head-up tilt test. The electrocardiographic QT interval was corrected for heart rate (HR) according to Fridericia's equation (QTc). In addition, cardiovascular reactivity was assessed based on blood pressure and HR changes and was expressed as the 'hemodynamic instability score' (HIS).
The average supine QTc in FM was 417 ms (SD 25) versus 372 ms (SD 22) in CFS (p<0.0001); the supine QTc cut-off <385.7 ms was 79% sensitive and 87% specific for CFS vs. FM. The average QTc at the 10th minute of tilt was 409 ms (SD 18) in FM versus 367 ms (SD 21) in CFS (p<0.0001); the tilt QTc cut-off <383.3 ms was 71% sensitive and 91% specific for CFS vs. FM. The average HIS in FM patients was -3.52 (SD 1.96) versus +3.21 (SD 2.43) in CFS (p<0.0001).
A relatively short QTc and positive HIS characterize CFS patients and distinguish them from FM patients. These data may support the contention that FM and CFS are separate disorders.
[Ed. Note: This is another study noting the differences between CFS and FM.]
Arroll, MA and Senior, V. Individuals' experience of chronic fatigue syndrome/myalgic encephalomyelitis: An interpretative phenomenological analysis. Psychology & Health, 2008, 23, 4, 443-458.
CFS/myalgic encephalomyelitis (CFS/ME) is a condition of unknown aetiology that consists of symptoms such as fatigue, muscle and joint pain, gastric problems and a range of neurological disturbances. Due to the fact that these symptoms are complaints that most individuals will experience to a varying degree, it seems pertinent to investigate the processes by which those with CFS/ME conceptualise their symptoms and the experience of reaching a diagnosis.
Participants were recruited from local CFS/ME support groups. Eight semi-structured telephone interviews were conducted and transcribed, and the verbatim transcriptions were analysed according to interpretative phenomenological analysis (IPA). Six distinct themes were uncovered that illustrated the participants' experience and perception of their symptoms. These included symptomatology and illness course, interference with daily and working life, frequency of symptoms, external information, diagnosis and treatment. The findings were discussed in terms of internal and external cues related to symptom perception and the discovery that the possession of a diagnosis did not necessarily signify the end of the journey.
Deary, V. A precarious balance: Using a self-regulation model to conceptualize and treat chronic fatigue syndrome. British Journal of Health Psychology, 2008, 13, 2, 231-236.
The problem posed by CFS to the affected individual can be conceptualized, using Leventhal's common sense model, as a health threat to be encoded and coped with accordingly. The current paper adopts an alternative use of self-regulation theory. It is hypothesized that in CFS the health threat is no longer the illness, but anything that threatens to disrupt a precarious accommodation to it. It is argued that attempts at threat regulation may become inadvertently self-defeating, promoting the threats they attempt to diminish. Evidence is presented for homeostatic mechanisms in physiological, neurocognitive and affective domains, and for their potential to become locked in vicious circles. It is further argued that illness attributions, rather than being independent cognitive processes, may be intimately linked with emotional and somatic processes. Damasio's somatic marker hypothesis is used to suggest ways in which the self-regulation of highly interconnected somatic, affective, and cognitive states may be substantially implicated in the maintenance of CFS. This perspective is used to reconsider effective treatment and to suggest new interventions. The self-regulation model is a potentially powerful explanatory framework for the consideration and treatment of CFS and medically unexplained symptoms in general.
Extracts: A predominant theme in the self-help literature on CFS is the ‘energy budget’ (Packer, Brink, & Sauriol, 1995) or the ‘energy envelope’ (Pesek, Jason, & Taylor, 2000). These theories suggest that the affected individual has a limited fund of energy that must be carefully managed. Both over- and under-activity are likely to provoke a worsening of the condition (Taylor, 2004) necessitating a narrowed range of activity. As such the ‘danger’ in CFS/ME may no longer be the illness itself, adjustment to which has become the status quo, but anything that threatens to force the individual to work outside these narrow limits. The problem CFS poses for the individual is thus primarily one of homeostasis, that is resistance to variance. In the following we will apply this hypothesis of a precarious homeostasis as the main ‘danger’ to be regulated in CFS, and see if this can usefully illuminate both our understanding and treatment of this condition... Thus in CFS, core homeostatic mechanisms may be in operation which, whilst adaptive in intent, may serve to maintain a narrow range of variance through defensive withdrawal, and maintain symptoms through an aroused res-ponding to anything that threatens the status quo... In the individual with CFS, where the parameters of safety are narrow and the range of threat broad, there will be an extensive array of established somatic markers of threats to homeostasis. In response to novel stimuli, these markers will activate feeling states, providing important feedback to the individual about the threat potential of the current or anticipated state. This latter point is important, for, as argued by Hayes, Strosahl, and Wilson (1999) in their notion of stimulus equivalence, the representation of a thing can evoke the same physiological reaction as the thing itself...
In CFS this raises the possibility that not only actual threats, but also the anticipation of them, could evoke a somatic reaction... The best evidence is for interventions that gradually increase physical activity. From the self-regulation perspective outlined above, this may work by not only reversing deconditioning (Clarke & White, 2005) or by desensitizing the fear of activity, (Moss-Morris, 2003), but also by acting as a graded exposure to avoided interoceptive sensations (fatigue and pain) and emotions, allowing them to be somatically remarked as benign, thus terminating self-defeating attempts to regulate experience of them. Also, in recovery, there may be a cognitive shift that has so far been only implicit in the literature. Self-regulation models are goal-driven, with the goal of the CFS sufferer being the maintenance of a precarious homeostasis. CBT and graded exercise approaches encourage patients to switch their evaluation of themselves and their progress from how they are feeling to what they are able to do, despite symptoms. In the terminology of self-regulation, these approaches may work by changing the reference value from symptom avoidance to general well-being... Self-regulation, and the potential of self-regulating mechanisms to become stuck in recursive and degenerating loops, may lie at the heart of the experience of MUS in general (Deary et al., 2007). Leventhal’s model provides a coherent framework for further investigating this hypothesis.
[Ed. Note: The author’s arguments rely on a number of assumptions. These include the notion of a universal maladaptive response to fatigue (i.e. avoidance) and that in relation to a single underlying pathological process, the current ‘absence of evidence’ amounts to ‘evidence of absence’ (this ignores the heterogeneity of the population and findings of ongoing pathology in subsets.) He also assumes that the fatigue is largely a result of deconditioning, ignoring evidence to the contrary and leaving readers with the impression that the decisions regarding activity are primarily guided by a misinterpretation of post-exertional symptoms and fear. He misrepresents pacing, as the best known versions do not advocate operating below one’s capabilities (see Goudsmit and Howes, below). In contrast to GET, pacing acknowledges the post-exertional abnormalities in muscle and immune function documented in subsets, which indicate that for many, a fear of a relapse if they exceed their tolerance levels has a realistic (physiological) basis. Leventhal’s model may not be useful in relation to complex illnesses such as CFS and does not adequately deal with heterogeneous populations and individual differences. Lazarus’ theory of coping and stress may be more helpful, both in terms of understanding the illness-as-lived and in relation to management.]
See also editorial by Wearden and Peters (ibid, 189-193). “In CFS, physiological dysregulation (e.g. cardiovascular deconditioning, sleep disturbance, hypothalamo–pituitary–adrenal axis disturbance) both influences and is maintained by interacting cognitive, behavioural, and emotional factors.”
Dickson, A., Knussen, C and Flowers, P. 'That was my old life; it's almost like a past-life now': Identity crisis, loss and adjustment amongst people living with chronic fatigue syndrome. Psychology & Health, 2008, 23, 4, 459-476.
Individual in-depth interviews were conducted with 14 people with CFS (CDC criteria ’94). The interviews centred on the experience of living with the condition from the participants' own perspectives. All interviews were transcribed verbatim and were analysed using Inter-pretative Phenomenological Analysis. Three inter-related themes were presented: 'Identity crisis: agency and embodiment'; 'Scepticism and the self' and 'Acceptance, adjustment and coping'.
Participants reported an ongoing sense of personal loss characterised by diminishing personal control and agency. An inability to plan for the future and subsequent feelings of failure, worthlessness and insignificance ensued. Scepticism in the wider social environment only heightened the consequential identity crisis. The importance of acceptance for adjusting to a life with CFS was highlighted. The findings are discussed in relation to extant literature and issues for health psychology are raised.
Jason, LA., Torres-Harding, S., Brown, M., Sorenson, M., Donalek, J., Corradi, K., Maher, K and Fletcher, MA. Predictors of change following participation in non-pharmacologic interventions for CFS. Tropical Medicine and Health, 2008, 36, 1, 23-32.
The purpose of this study was to evaluate predictors of change in physical function in individuals diagnosed with CFS following participation in nurse delivered, non-pharmacologic interventions. Participants diagnosed with CFS (CDC criteria ’94) were randomly assigned to one of four, 6-month interventions including CBT, cognitive therapy, anaerobic exercise, or a relaxation control group.
Baseline measures including immune function, actigraphy, time logs, sleep status, and past psychiatric diagnosis significantly differentiated those participants who demonstrated positive change over time from those who did not. Baseline current psychiatric status was not related to recovery but a past history of psychiatric disorder was associated with a good outcome. Those who improved had more baseline energy and less daytime dysfunction. More improvement occurred in the low or moderately active groups. There were also immunological differences, e.g., those who improved had a significantly lower per cent and number of B cells (CD19+). Those with a Type 2 immune response did not tend to improve.
Understanding how patient subgroups differentially respond to non-pharmacologic interventions might provide insights into the pathophysiology of this illness.
Harvey, SB., Wadsworth, M., Wessely, S and Hotopf, M. Etiology of chronic fatigue syndrome: testing popular hypotheses using a National Birth Cohort Study. Psychosomatic Medicine, 2008 Mar 31 [Epub ahead of print]. DOI: 10.1097/PSY.0b013e31816a8dbc.
The aims were to review the aetiology of CFS and test hypotheses relating to immune system dysfunction, physical deconditioning, exercise avoidance, and childhood illness experiences, using a large prospective birth cohort.
A total of 4779 participants from the Medical Research Council's National Survey of Health and Development were prospectively followed for the first 53 years of their life with >20 separate data collections. Information was collected on childhood and parental health, atopic illness, levels of physical activity, fatigue, and participant's weight and height at multiple time points. CFS was identified through self-report during a semi-structured interview at age 53 years with additional case notes review.
Of 2983 participants assessed at age 53 years, 34 (1.1%, 95% Confidence Interval 0.8-1.5) reported a diagnosis of CFS (65% of these were diagnosed by a doctor). Those who reported CFS were no more likely to have suffered from childhood illness or atopy. Increased levels of exercise throughout childhood and early adult life and a lower body mass index were associated with an increased risk of later CFS. Participants who later reported CFS continued to exercise more frequently even after they began to experience early symptoms of fatigue.
Individuals who exercise frequently are more likely to report a diagnosis of CFS in later life. This may be due to the direct effects of this behavior or associated personality factors. Conti-nuing to be active despite increasing fatigue may be a crucial step in the development of CFS.
Gräns, H., Evengård, B and Nilsson, P. Transcriptome analysis of peripheral blood mononuclear cells from patients with chronic fatigue syndrome. Journal of Chronic Fatigue Syndrome, 2007, 14, 3, 7-25. The etiology and pathophysiology of CFS are to a large degree unknown. Since much remains unclear about CFS we wanted to investigate transcript expression levels in peripheral blood mononuclear cells to identify genes that are involved in CFS. Transcript expression profiles for 20 CFS patients (CDC criteria ’94) were compared with 14 healthy controls using microarray technology. Results were verified with real-time PCR. We identified significantly differentially expressed genes comparing a female CFS patient subgroup with gradual illness onset and no previously documented infection, with female healthy controls. We also created a list of genes with indicated, but not verified, expression differences from comparisons between other subgroups and healthy controls. These genes are candidates for further study of potential involvement in CFS. Our results stress the necessity of subgrouping the heterogeneous CFS patient cohort. The mRNA expression differences identified here may be causal factors for the illness or symptoms observed in these patients, or a result of altered functions of other cellular components involved in the illness. The role of these genes in the CFS pathology needs further investigation. [Ed. Note: The selection of patients who did not have an acute, post-viral onset means that the findings cannot be generalised to this group.]GENETICS
Knoop, H., Stulemeijer, M., de Jong, LW., Fiselier, TJ and Bleijenberg, G. Efficacy of cognitive behavioral therapy for adolescents with chronic fatigue syndrome: Long-term follow-up of a randomized, controlled trial. Pediatrics, 2008, 121, 3, e619-25.
The purpose of this work was to assess the long-term outcome of adolescents with CFS who received CBT and to determine the predictive value of fatigue severity and physical impairments of the adolescent and the fatigue severity of the mother at baseline for the outcome of the treatment at follow-up.
Sixty-six adolescent patients with CFS who previously participated in a randomized, controlled trial that showed that CBT was more effective than a waiting-list condition in reducing fatigue and improving physical functioning were contacted for a follow-up assessment. Fifty participants of the follow-up study had received CBT for CFS (32 formed the CBT group in the original trial, and 18 patients received CBT after the waiting period, though three ‘withdrew’ and did not complete therapy). The remaining 16 patients had refused CBT after the waiting period. The main outcome measures were fatigue severity (Checklist Individual Strength), physical functioning (Short-Form General Health Survey), and school attendance.
Data were complete for 61 patients at follow-up (CBT: 47 patients; no-treatment group: 14 patients). The mean follow-up time was 2.1 years. There was no significant change in fatigue severity between post-treatment and follow-up in the CBT group. However, there was a significant further increase in physical functioning and school attendance (10% increase). The adolescents in the CBT group were significantly less fatigued and significantly less functionally impaired and had higher school attendance at follow-up than those in the no-treatment group. Fatigue severity of the mother was a significant predictor of treatment outcome.
The positive effects of CBT in adolescents with CFS are sustained after CBT. Higher fatigue severity of the mother predicts lower treatment outcome in adolescent patients.
http://pediatrics.aappublications.org/cgi/reprint/121/3/e619
[Ed. Note: 31-50% of the waiting list controls showed change, compared to 64-74% who received CBT. The reasons for the withdrawal were not given but it is alleged that adolescents in Nijmegen showing signs of adverse reactions were not invited back for further treatment.]
Walach, H., Bosch, H., Lewith, G., Naumann, J., Schwarzer, B., Falk, S., Kohls, N., Haraldsson, E., Wiesendanger, H., Nordmann, A., Tomasson, H., Prescott, P and Bucher, HC. Effectiveness of distant healing for patients with chronic fatigue syndrome: A randomised controlled partially blinded trial (EUHEALS). Psychotherapy and Psychosomatics, 2008, 77, 158-166.
Distant healing, a form of spiritual healing, is widely used for many conditions but little is known about its effectiveness. In order to evaluate distant healing in patients with a stable chronic condition, we randomised 409 patients with CFS or idiopathic CFS (Oxford and CDC criteria ’94) from 14 private practices for environmental medicine in Germany and Austria in a two by two factorial design to immediate versus deferred (waiting for 6 months) distant healing. Half the patients were blinded and half knew their treatment allocation. Patients were treated for 6 months and allocated to groups of 3 healers from a pool of 462 healers in 21 European countries with different healing traditions. Change in Mental Health Component Summary (MHCS) score (from the SF-36) was the primary outcome and Physical Health Component Summary score (PHCS) the secondary outcome.
This trial population had very low quality of life and symptom scores at entry. There were no differences over 6 months in post-treatment MHCS scores between the treated and untreated groups. There was a non-significant outcome (p=0.11) for healing with PHCS (1.11; 95% CI -0.255 to 2.473 at 6 months) and a significant effect (p=0.027) for blinding; patients who were unblinded became worse during the trial (-1.544; 95% CI -2.913 to -0.176). We found no relevant interaction for blinding among treated patients in MHCS and PHCS. Expectation of treatment and duration of CFS added significantly to the model.
In patients with CFS, distant healing appears to have no statistically significant effect on mental and physical health but the expectation of improvement did improve outcome.
Goudsmit, EM and Howes, S. Pacing: A strategy to improve energy management in chronic fatigue syndrome. Health Psychology Update, 2008, 17, 1, 46-52.
The recently published NICE guidelines for the management of CFS advocated three cognitive-behavioural interventions (NICE, 2007). They were not able to recommend pacing, a strategy to manage limited energy levels and avoid exertion-related symptomatology, due to a lack of information in the scientific literature. In this article, we introduce the two main versions of pacing being offered to patients, review their indications and limitations, and summarise the scientific evidence supporting its use, particularly as part of a multi-disciplinary rehabilitation programme.
[Ed. Note: The HPU is published by the British Psychological Society, Division of Health Psychology.]
Nijs, J., Paul, L and Wallman, K.
Chronic fatigue syndrome: An approach combining self-management with graded exercise to avoid exacerbations. Journal of Rehabilitation Medicine, 2008, 40, 4, 241-247.Controversy regarding the aetiology and treatment of patients with CFS continues among the medical professions. The Cochrane Collaboration advises practitioners to implement graded exercise therapy (GET) for patients with CFS using cognitive behavioural principles. Conversely, there is evidence that exercise can exacerbate symptoms in CFS, if too-vigorous activity promotes immune dysfunction, which in turn increases symptoms. When designing and implementing an exercise programme for CFS, it is important to be aware of both of these seemingly opposing viewpoints in order to deliver a programme with no detrimental effects on the pathophysiology of the condition.
Using evidence from both the biological and clinical sciences, this paper explains that GET for people with CFS can be undertaken safely with no detrimental effects on the immune system. Exercise programmes should be designed to cater for individual physical capabilities and should take into account the fluctuating nature of symptoms. In line with cognitive behaviourally and graded exercise-based strategies, self-management for people with CFS involves encouraging patients to pace their activities and respect their physical and mental limitations, with the ultimate aim of improving their everyday functioning.
[Ed. Note: This paper promotes pacing consistent with the version devised by Goudsmit and Howes. However, the text contains a number of misleading statements. For example, the authors claim that there is no evidence that GET/exercise causes harm. However, the relatively high drop out rates in Prins et al are difficult to attribute to positive therapeutic effects. Moreover, other studies and surveys have reported adverse effects following CBT/GET. Also, there is a suggestion that moderate or severe exercise does not impair cognitive performance. This is inconsistent with the results of Blackwood, SK et al., Journal of Neurology, Neurosurgery and Psychiatry, 1998, 65, 541-546, and LaManca, JJ et al., American Journal of Medicine, 1998, 105, 3A, 59s-65s. Finally, the authors note that pacing on its own is being assessed in the PACE trial. In fact, this study is evaluating adaptive pacing therapy, which is a combination of pacing and GET. Thus patients are encouraged to continue with their regime even if unwell, on the assumption that adverse effects are a result of deconditoning. This is contrary to the principle of pacing where symptoms are perceived as a sign to cut back or stop. See also Wallman et al 2004).]
Nijs, J and Frémont, M. Intracellular immune dysfunction in myalgic encephalomyelitis/chronic fatigue syndrome: state of the art and therapeutic implications. Expert Opinion on Therapeutic Targets, 2008, 12, 3, 281-289.
Evidence in support of intracellular immune dysfunctions in people with myalgic encephalomyelitis (ME)/CFS is accumulating, but few studies have addressed intracellular immunity as a potential therapeutic target. This paper provides an overview of our present understanding of intracellular immunity in ME/CFS, to relate the intracellular immune dysfunctions to other aspects of the illness like decreased natural killer cell function, the presence of infections and poor exercise performance, and to point to potential therapeutic targets.
From the scientific literature, it is concluded that proteolytic cleavage of the native RNase L enzyme is characteristic of the dysregulation of intracellular immunity in people with ME/CFS, but the origin of the dysregulation is speculative. There is increasing evidence for immune cell apoptosis and upregulation of various aspects of the 2'-5' oligoadenylate (2-5A) synthetase/RNase L pathway in ME/CFS. This review provides the theoretical rationale for conducting studies examining the effectiveness of direct or indirect drug targeting of the 2-5A synthetase/RNase L pathway in ME/CFS patients.
Abdel-Khalek, AM. Chronic fatigue syndrome and its association with obsession compulsion among a non-clinical sample using questionnaires. Journal of Chronic Fatigue Syndrome, 2007, 14, 3, 89-100.
The present study investigated the possible association between the CFS and Obsession Compulsion (OC). A non-clinical sample of 427 volunteer Kuwaiti male and female college students was recruited. They completed the Arabic Scale of CFS (ASCFS) and the Arabic Scale of Obsession Compulsion (ASOC)... It is worth noting that those undergraduates were neither disturbed clinical cases nor diagnosed institutionalized patients, and that none stated that they suffered from CFS. Rather, they were young adults, and presumably healthy people in general. However, most of them had just CFS-like symptoms in different degrees.
Females had significantly higher mean score on the ASCFS than did their male counterparts. All the inter-correlations between the 20 items as well as the total score of the ASCFS were statistically significant (p<0.01) with the total ASOC score in males and females. It was concluded that there is an obsessive compulsive element in CFS, and both disorders share specific common elements.
[Ed. Note: The participants in this study did not have CFS and the current criteria’s reliance on fatigue and four other common symptoms mean one can not exclude people experiencing chronic stress which could explain the association with OCD (the latter leading to the former). In clinical terms, patients are usually too exhausted to maintain tiring activities such as those commonly reported in OCD. There is therefore no justification for their statement that “It is safe to conclude, on the one hand, that there may be an OC element in CFS.”]
Bassi, N., Amital, D., Amital, H., Doria, A and Shoenfeld, Y. Chronic fatigue syndrome: characteristics and possible causes for its pathogenesis. Israel Medical Association, 2008, 10, 1, 79-82.
CFS is a heterogeneous disorder with unknown pathogenesis and etiology, characterized by disabling fatigue, difficulty in concentration and memory, and concomitant skeletal and muscular pain. Several mechanisms have been suggested to play a role in CFS, such as excessive oxidative stress following exertion, immune imbalance characterized by decreased natural killer cell and macrophage activity, immunoglobulin G subclass deficiencies (IgG1, IgG3) and decreased serum concentrations of complement component. Autoantibodies were also suggested as a possible factor in the pathogenesis of CFS. Recent studies indicate that anti-serotonin, anti-microtubule-associated protein 2 and anti-muscarinic cholinergic receptor 1 may play a role in the pathogenesis of CFS. It has been demonstrated that impairment in vasoactive neuropeptide metabolism may explain the symptoms of CFS.
Blazquez, A., Ruiz, E., Vazquez, A., de Sevilla, TF., Garcia-Quintana, A., Garcia-Quintana, J and Alegre, J. Sexual dysfunction as related to severity of fatigue in women with CFS. Journal of Sexual & Marital Therapy, 2008, 34, 3, 240-247.
The aim of this study was to assess sexual function in women with CFS. The study included 27 women, aged 20 to 45 years, with CFS (CDC criteria ’88 or ’94) and 15 healthy female controls. Sexual function was measured with the Golombok Rust Inventory of Sexual Satisfaction (GRISS) questionnaire and five clinical questions. In the patient group, total fatigue impact scale (FIS) score correlated with the GRISS satisfaction (r:-0.471, p<.005), avoidance (r:0.632, p<.001) and sensuality (r:-0.445, p=.008) subscales. The GRISS satisfaction, avoidance, and sensuality subscale results and the fact of seeing the sexual act as a negative experience correlated with the intensity of fatigue in women with CFS
Ciccone, DS., Weissman, L and Natelson, BH. Chronic fatigue syndrome in male gulf war veterans and civilians: A further test of the single syndrome hypothesis. Journal of Health Psychology, 2008, 13, 4, 529-536.
Different modes of fatigue onset in male Gulf War veterans versus male civilians raise the possibility that CFS may not be a single disease entity. We addressed this issue by comparing 45 male veterans with CFS to 84 male civilians who satisfied identical case criteria (non-severe CFS: CDC criteria ’94, severe: CDC criteria ’88). All were evaluated for FM, multiple chemical sensitivity (MCS) and psychiatric comorbidity. Measures included the MOS-SF and DIS.
CFS was more likely to present in a sudden flu-like manner in civilians than veterans (p<.01) and co-morbid FM was more prevalent in civilians (p<.01). There was no difference in incidence of MCS. The civilians suffered more disability which was not related to co-morbid disorders.
These findings question the assumption that all patients with CFS suffer from the same underlying disorder.
Cho, HJ., Rossi Menezes, P., Bhugrad, D and Wessely, S.
The awareness of chronic fatigue syndrome: A comparative study in Brazil and the United Kingdom. Journal of Psychosomatic Research, 2008, 64, 4, 351-355.Short communication. While in many Western affluent countries there is widespread awareness of CFS, also known as ME, little is known about the awareness of CFS/ME in low- and middle-income countries. We therefore compared the awareness of CFS in Brazil and the United Kingdom.
Recognition and knowledge of CFS were assessed among 120 Brazilian specialist doctors in two major university hospitals using a typical case vignette of CFS. We also surveyed 3914 and 2435 consecutive attenders in Brazilian and British primary care clinics, respectively, concerning their awareness of CFS. When given a typical case vignette of CFS, only 30.8% of Brazilian specialist doctors mentioned chronic fatigue or CFS as a possible diagnosis, a proportion substantially lower than that observed in Western affluent countries. Similarly, only 16.2% of Brazilian primary care attenders were aware of CFS, in contrast to 55.1% of their British counterparts (p<.001). This difference remained highly significant after controlling for patients' sociodemographic and socioeconomic characteristics (p<.001).
The most frequently mentioned cause for the case vignette was either stress/overworking (30.0%) or psychological problems (30.0%), followed by hormonal alteration (13.6%), virus (11.5%), immunological alteration (7.0%), and other (7.8%). The treatment option most frequently indicated for the case was antidepressants (24.1%), followed by exercise therapy (17.3%), counseling or traditional psychotherapy (17.3%), relaxation (13.9%), CBT (11.4%), rest (4.0%), nutritional supplement (2.2%), immunotherapy (1.5%), hormones (1.2%), antiviral (0.6%), homeopathy (0.6%), and other (5.9%).
The awareness of CFS was substantially lower in Brazil than the United Kingdom. The observed difference may influence patients' help-seeking behaviour and both doctors' and patients' beliefs and attitudes in relation to fatigue-related syndromes. Attempts to promote the awareness of CFS should be considered in Brazil, but careful plans are required to ensure the delivery of sound evidence-based information.
Letter. The authors investigated the composition of the aerobic and anaerobic microflora, the number of staphylococcal spp, Clostridium spp, E. coli and C. albicans using culture techniques. Faecal samples were collected from 20 patients with CFS in the acute phase of the illness and while in remission, and from 19 healthy controls.
A significantly higher number of C. albicans was found in CFS patients when in the acute phase of illness compared with when in remission Chronic intestinal candidiasis, mucous membrane overgrowth of C. albicans, has previously been suggested to be a causal factor in CFS. It is also possible that increased levels of C. albicans function as an indicator of an ecological disturbance that plays an important role in the symptom profile of the illness.
Fulle, S., Pietrangelo, T., Mancinelli, R., Saggini, R and Fanò, G. Specific correlations between muscle oxidative stress and chronic fatigue syndrome: A working hypothesis. Journal of Muscle Research and Cell Motility, 2007, 28, 6, 355-362.
The role of oxidative stress in CFS is an emerging focus of research due to evidence of its association with some pathological features of this syndrome. New data collectively support the presence of specific critical points in the muscle that are affected by free radicals and in view of these considerations, the possible role of skeletal muscle oxidative imbalance in the genesis of CFS is discussed.
Godfrey, E., Chalder, T., Ridsdale, L., Seed, P and Ogden, J. Investigating the ‘active ingredients’ of cognitive behaviour therapy and counselling for patients with chronic fatigue in primary care: Developing a new process measure to assess treatment fidelity and predict outcome. British Journal of Clinical Psychology, 2007, 46, 253-272.
The aim of this study was to develop a brief measure of the therapy process and use it to examine which therapeutic ingredients were associated with outcome in a sample of patients from a randomized controlled trial (RCT) of CBT versus counselling for patients with chronic fatigue in primary care. Some patients fulfilled criteria for CFS. The trials had shown little difference between the therapies.
The data for this study were collected alongside a RCT in primary care and included audiotaped therapy sessions. These tapes were assessed by two independent raters using a newly devised measure in order to evaluate therapy process and its relationship with outcome. Tapes from 71 patients participating in the RCT were assessed to form the basis of the process analysis. Outcome was self-reported fatigue symptoms at 6 months follow-up.
The process measure showed that although the treatments could be distinguished, there was some overlap between them. The key predictor of a good fatigue outcome was emotional processing, including the expression, acknowledgement and acceptance of emotional distress.
Hobday, RA., Thomas, S., O'Donovan, A., Murphy, M and Pinching, AJ. Dietary intervention in chronic fatigue syndrome. Journal of Human Nutrition and Dietetics, 2008, 21, 2, 141-149.
Anecdotal reports and books have been published linking an over growth of Candida Albicans with CFS, suggesting dietary change as a treatment option. Little scientific data has been published to validate this controversial theory. This study aims to determine the efficacy of dietary intervention on level of fatigue and quality of life (QoL) in individuals with CFS.
A 24-week randomized intervention study was conducted with 52 individuals diagnosed with CFS. Patients were randomized to either a low sugar low yeast (LSLY) or healthy eating (HE) dietary interventions. Primary outcome measures were fatigue as measured by the Chalder Fatigue Score (14 item) and QoL measured by Medical Outcomes Survey Short Form-36.
A high drop out rate occurred with 13 participants not completing the final evaluation (7HE/6LSLY). Intention to treat analysis showed no statistically significant differences on primary outcome measurements. In this randomized control trial, a LSLY diet appeared to be no more efficacious on levels of fatigue or QoL compared to HE. Given the difficulty with dietary compliance experienced by participants, especially in the LSLY group, it would appear HE guidance is a more pragmatic approach than advocating a complicated dietary regime.
[Ed. Note: The diet was based on the views of an ‘alternative’ practitioner and is far more extreme that that proposed by physicians specialising in dysbiosis. There were no details in-dicating the presence of symptoms suggestive of candida and no supportive tests appear to have been done, e.g. for markers in blood or overgrowth in the small bowel. The post-treatment MOS-PF scale indicates severe disability in both groups which neither diet alleviated.]
Holtorf, K. Diagnosis and treatment of hypothalamic-pituitary-adrenal (HPA) axis dysfunction in patients with chronic fatigue syndrome (CFS) and fibromyalgia (FM). Journal of Chronic Fatigue Syndrome, 2007, 14, 3, 59-88.
Review. There is controversy regarding the incidence and significance of HPA axis dysfunction in CFS and FM. Studies that utilize central acting stimulation tests, including corticotropin-releasing hormone (CRH), insulin stress testing (IST), d-fenfluramine, ipsapirone, interleukin-6 (IL-6) and metyrapone testing, have demonstrated that HPA axis dysfunction of central origin is present in a majority of these patients. However, ACTH stimulation tests and baseline cortisol testing lack the sensitivity to detect this central dysfunction and have resulted in controversy and confusion regarding the incidence of HPA axis dysfunction in these conditions and the appropriateness of treatment. While both CFS and FM patients are shown to have central HPA dysfunction, the dysfunction in CFS is at the pituitary-hypothalamic level while the dysfunction in FM is more related to dysfunction at the hypothalamic and supra-hypothalamic levels. Because treatment with low physiologic doses of cortisol (<15 mg) has been shown to be safe and effective and routine dynamic ACTH testing does not have adequate diagnostic sensitivity, it is reasonable to give a therapeutic trial of physiologic doses of cortisol to the majority of patients with CFS and FM, especially to those who have symptoms that are consistent with adrenal dysfunction, have low blood pressure or have baseline cortisol levels in the low or low-normal range.
[Ed. Note: The author summarises findings from two unpublished studies supporting the use of low levels cortisol.]
Kerr, JR and Mattey, DL. Preexisting psychological stress predicts acute and chronic fatigue arthritis following symptomatic parvovirus B19 infection. Clinical Infectious Diseases, 2008, 46, 9, e83-87.
Psychological stress is thought to be an important factor in the pathogenesis of CFS/ME. Therefore, we sought to examine this relationship in the context of parvovirus B19 infection.
Thirty-nine patients with laboratory-documented acute parvovirus B19 infection were asked to complete questionnaires on negative life events, perceived stress, and negative affect relevant to the time of onset of parvovirus infection and during the preceding 12 months. These scores were combined into an overall stress index, which was then examined for associations with particular parvovirus-associated symptoms at acute infection and during the ensuing 1-3 years. Additional characteristics monitored included presence of parvovirus antibodies and nucleic acid, cortisol level, dehydroepiandrosterone level, autoantibodies, levels of a range of serum cytokines, and human leukocyte antigen class I and II alleles.
Stress index was significantly associated with development of fatigue during the acute phase of parvovirus B19 infection and also with chronic fatigue and arthritis occurring 1-3 years following acute parvovirus B19 infection. Logistic regression that included all clinical variables indicated that a high stress index at the time of onset of infection was the primary predictor of CFS/ME 1-3 years following acute parvovirus B19 infection (odds ratio, 25.7; 95% confidence interval, 1.7-121.9; p=.005).
We report a highly significant association between psychological stress and development of acute and chronic fatigue and arthritis several years following laboratory-documented acute parvovirus B19 infection.
[Ed. Note: A similar relationship between stress and illness has also been found in relation to MS. It is possible that the patients recall events more accurately or perceive them as more significant and this is consistent with the failure to find a correlation with cortisol - a sensitive measure of stress. Other observations e.g. Ciccone et al., found no relationship between deployment stress and CFS, and there appears to be no higher prevalence in stressed communities e.g. in holocaust survivors and their children. The similarity between the symptoms required for diagnosis of CFS (CDC criteria ’94) and chronic stress makes it difficult to assess whether a patient is suffering from one or the other, or both. Only 5 patients were suffering from CFS at follow-up, so the findings should be interpreted with caution.]
Jason, LA., Benton, MC., Valentine, L., Johnson, A and Torres-Harding, S.
The economic impact of ME/CFS: individual and societal level costs. Dynamic Medicine, 2008, 7:6,DOI:10.1186/1476-5918-7-6.ME/CFS is characterized by debilitating fatigue in addition to other physical and cognitive symptoms. It is estimated to affect over 800,000 adults in the U.S. ME/CFS often results in diminished functionality and increased economic impact. The economic impact of an illness is generally divided into two categories: direct and indirect costs. Despite high prevalence rates and the disabling nature of the illness, few studies have examined the costs of ME/CFS at the individual and societal level. The current study used community and tertiary samples to examine the direct costs of ME/CFS.
Using archival data, Study 1 examined the direct cost of ME/CFS (CDC criteria ’94) in a community-based sample in Chicago. Study 2 estimated the direct cost of ME/CFS in a tertiary sample in Chicago. Both Study 1 and Study 2 assessed direct costs using office visit costs, medical test costs, and medication costs.
For Study 1, the annual direct total cost per ME/CFS patient was estimated to be $2,342, with the total annual direct cost of ME/CFS to society being approximately $2 billion. In Study 2, the annual direct was estimated to be $8,675 per ME/CFS patient, with the total annual direct cost of ME/CFS to society being approximately $7 billion. Using ME/CFS prevalence data and indirect costs estimates from Reynolds et al., 2004, the direct and indirect cost of ME/CFS to society was estimated to be $18,677,912,000 for the community sample and $23,972,300,000 for the tertiary sample. These findings indicate that whether or not individuals are recruited from a community or tertiary sample, ME/CFS imposes substantial economic costs.
Libman, E., Creti, L., Rizzo, D., Jastremski, M., Bailes, S and Fichten, CS. Descriptors of fatigue in chronic fatigue syndrome. Journal of Chronic Fatigue Syndrome, 2007, 14, 3, 37-45.
The objective was to explore how individuals with CFS describe their fatigue experience and examine how this differs from descriptions of fatigue in healthy controls. Fifty-two individuals with CFS and 27 controls listed words that described their fatigue. These words were grouped into 18 categories.
Individuals with CFS used more categories to describe their fatigue and more descriptors within each category. The most popular category used by both groups was energy depletion/physical weakness. CFS participants also experienced their fatigue as limiting their ability to function, frustrating, permanent/persistent, out of their control, depressing, and pervading all aspects of their lives. Controls reported that when they experienced fatigue, it was temporary, and they felt unmotivated, sleepy, and comfortable.
The multidimensional descriptive pattern characterizing the fatigue of individuals with CFS differs dramatically from the experienced fatigue of healthy individuals, suggesting their "language of fatigue" has a distinctive quality.
Lowry, TJ and Pakenham, KI. Health-related quality of life in chronic fatigue syndrome: Predictors of physical functioning and psychological distress. Psychology, Health & Medicine, 2008, 13, 2, 222–238.
This study investigated health-related quality of life (HRQoL; physical functioning and psychological distress) in an Australian CFS population. The aims of the study were to compare HRQoL in those with CFS to the normal population, and to investigate the extent to which sociodemographic (age, gender, partner status, education), illness-related (illness duration, symptom frequency), and fatigue severity (physical, mental) variables predicted HRQoL.
A total of 139 people meeting CFS criteria completed questionnaires. HRQoL was assessed using standardised measures of distress and physical functioning. Compared with norms, those with CFS obtained significantly lower scores on all physical functioning areas, whereas 63% of participants reported clinically significant psychological distress. Hierarchical regression analyses indicated that physical fatigue severity and symptom frequency were the strongest predictors of deficits in physical domain HRQoL. Physical HRQoL outcomes were also predicted by mental fatigue severity, older age, and female gender. All predictors were unrelated to psychological distress apart from weak positive associations with physical fatigue and symptom frequency. Results identify a potent set of predictors of HRQoL and show that CFS has a pervasive negative impact on quality of life, particularly physical and psychological functioning.
Meeus, M., Nijs, J., McGregor, N., Meeusen, R., De Schutter, G., Truijen, S., Frémont, M., Van Hoof, E and De Meirleir, K. Unravelling intracellular immune dysfunctions in chronic fatigue syndrome: Interactions between protein kinase R activity, RNase L cleavage and elastase activity, and their clinical relevance. In Vivo, 2008, 22, 1, 115-121.
This study examined the possible interactions between immunological abnormalities and symptoms in CFS. Sixteen CFS patients filled in a battery of questionnaires, evaluating daily functioning, and underwent venous blood sampling, in order to analyse immunological abnormalities. Ribonuclease (RNase) L cleavage was associated with RNase L activity (rs=0.570; p=0.021), protein kinase R (PKR) (rs=0.716; p=0.002) and elastase activity (rs=0.500; p=0.049). RNase L activity was related to elastase (rs=0.547; p=0.028) and PKR activity (rs=0.625; p=0.010). RNase L activity (rs=0.535; p=0.033), elastase activity (rs=0.585; p=0.017) and RNase L cleavage (rs=0.521; p=0.038) correlated with daily functioning.
This study suggests that in CFS patients an increase in elastase activity and subsequent RNase L cleavage is accompanied by increased activity of both the PKR and RNase L enzymes. RNase L and elastase activity are related to daily functioning, thus evidence supporting the clinical importance of these immune dysfunctions in CFS patients was provided.
Nijs, J., Zwinnen, K., Meeusen, R., de Geus, B and De Meirleir, K. Comparison of two exercise testing protocols in patients with chronic fatigue syndrome. Journal of Rehabilitation Research and Development, 2007, 44, 4, 553-560.
This study examined whether a linear exercise stress-testing protocol generated different peak exercise performance variables than a stepwise exercise testing protocol in patients with CFS. We conducted a comparative study with patients randomly allocated to one of two exercise testing protocols. Twenty-eight women with CFS completed two self-reported measures (the CFS Symptom List and the CFS Activities and Participation Questionnaire) and then performed until exhaustion either the linear or the stepwise exercise testing protocol with continuous monitoring of physiological variables (heart rate and oxygen uptake).
At baseline, we found no significant differences in demographic features and health status between groups. Based on ratio peak workload/peak oxygen uptake, mechanical efficiency was lower among the subjects performing the stepwise protocol (p=0.002). When we analyzed the mean linear regression slope values between oxygen uptake and workload from each subject's minute-by-minute exercise data points, we found that mechanical efficiency was lower among the subjects performing the stepwise protocol (p=0.039). Apart from mechanical efficiency, we found no differences in exercise performance data between groups (p>0.05).
Our results suggest that the difference between linear and stepwise exercise protocols cannot account for all discrepancies of previous studies on exercise performance data in women with CFS, but they do suggest that the nature of the exercise testing protocol influences mechanical efficiency in these patients. Further study is warranted.
Nijs, J., Adriaens, J., Schuermans, D., Buyl, R and Vincken, W. Breathing retraining in patients with chronic fatigue syndrome: A pilot study. Physiotherapy Theory and Practice, 2008, 24, 2, 83-94.
The study aimed to 1) examine the point prevalence of asynchronous breathing in CFS patients; 2) examine whether CFS patients with an asynchronous breathing pattern present with diminished lung function in comparison with CFS patients with a synchronous breathing pattern; and 3) examine whether one session of breathing retraining in CFS patients with an asynchronous breathing pattern is able to improve lung function.
Twenty patients fulfilling the diagnostic criteria for CFS were recruited for participation in a pilot controlled clinical trial with repeated measures. Patients presenting with an asynchronous breathing pattern were given 20-30 minutes of breathing retraining. Patients presenting with a synchronous breathing pattern entered the control group and received no intervention.
Of the 20 enrolled patients with CFS, 15 presented with a synchronous breathing pattern and the remaining 5 patients (25%) with an asynchronous breathing pattern. Baseline comparison revealed no group differences in demographic features, symptom severity, respiratory muscle strength, or pulmonary function testing data (spirometry). In comparison to no treatment, the session of breathing retraining resulted in an acute (immediately post-intervention) decrease in respiratory rate (p<0.001) and an increase in tidal volume (p<0.001). No other respiratory variables responded to the session of breathing retraining.
In conclusion, the present study provides preliminary evidence supportive of an asynchronous breathing pattern in a subgroup of CFS patients, and breathing retraining might be useful for improving tidal volume and respiratory rate in CFS patients presenting with an asynchronous breathing motion.
Sohl, SJ and Friedberg, F.
Memory for fatigue in chronic fatigue syndrome: Relationships to fatigue variability, catastrophizing, and negative affect. Behavioral Medicine, 2008, 34, 1, 29-38.Fatigue in CFS is usually assessed with retrospective measures rather than real-time momentary symptom assessments. In this study, the authors hypothesized that in participants with CFS, discrepancies between recalled and momentary fatigue would be related to catastrophizing, anxiety, and depression and to variability of momentary fatigue. They also expected that catastrophizing, anxiety, and depression would be associated with momentary fatigue.
The authors asked 53 adults with CFS (CDC criteria ’94) to carry electronic diaries for 3 weeks and record their experiences of momentary fatigue. The authors assessed participants' fatigue recall with weekly ratings and administered questionnaires for catastrophizing, depression, and anxiety.
Recall discrepancy was significantly related to the variability of momentary fatigue. In addition, catastrophizing, depression, and momentary fatigue were all significantly related to recall discrepancy. “Higher levels of catastrophizing and depression were predictive of more accurate recall of momentary fatigue.” The findings suggest that momentary fatigue in patients with CFS is related to modifiable psychological factors.
[Ed. Note: The participants were comparatively mildly affected. There was no control group to link the findings to CFS as opposed to chronic illness.]
Ulvestad, E. Chronic fatigue syndrome defies the mind-body-schism of medicine: New perspectives on a multiple realisable developmental systems disorder. Medicine, Health Care & Philosophy, 2008 Feb 21 [Epub ahead of print]. DOI: 10.1007/s11019-008-9126-2.
The author maintains that CFS can be properly understood only by taking an integrated perspective in which evolutionary, developmental and ecological aspects are considered. The integrative approach, supplemented by a complexity theory and psychoneuroimmunological research, is capable of explaining why there are so few structural aberrations to be found in CFS and why specific treatment is so difficult to establish. A major outcome of the in-vestigation, that all individuals with CFS are diseased in their own way, emphasises the need to study the development of personalised life histories. It also highlights an ethical dimension; personalised disease defies essentialist thinking on patient management. Another major outcome, which follows from the developmental systems perspective, is the dissolution of ontological mind-body dualism. This in turn allows for a methodological complementation of the biological and phenomenological approaches to knowledge. New research strategies that may help to resolve CFS, grounded in the revised perspective on individual development, are suggested.
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The importance of longitudinal as opposed to cross-sectional investigations was recently highlighted in an empirical study of healthy individuals in which sleep disturbances and fatiguing symptoms were associated with natural killer cell activity. The longitudinal design revealed significant changes that were masked by a large interpersonal variability in the cross-sectional design (Shakhar et al. 2007)... Interestingly, research on monozygotic twins discordant for CFS has pointed out that awareness of painful stimuli may be differentially experienced at the subjective level (Ullrich et al. 2007). Patients with CFS may thus experience a hypersensitivity problem.”
Van Weering, M., Vollenbroek-Hutten, MMR., Kotte, EM and Hermens, HJ. Daily physical activities of patients with chronic pain or fatigue versus asymptomatic controls. A systematic review. Clinical Rehabilitation, 2007, 21, 1007-1023.
Systematic review which included five studies on CFS. Results indicated lower activity levels than in healthy controls. The authors note that in general, subjective instruments of activity do not measure actual behaviour. There were notable differences between various groups including CFS and chronic pain.
Yiu, YM., Ng, SM., Tsui, YL and Chan, YL. A clinical trial of acupuncture for treating chronic fatigue syndrome in Hong Kong. Zhong Xi Yi Jie He Xue Bao (Journal of Chinese Integrative Medicine), 2007, 5, 6, 630-633. (In Chinese).
The objective was to evaluate the efficacy of acupuncture in treating CFS in Hong Kong. A single-blinded, randomized controlled trial design was adopted. Participants meeting inclusion criteria were randomly assigned to a treatment and a control group according to 1:1 ratio, resulting in an effective sample size of 99, with 50 and 49 patients in treatment and control group respectively. The same set of acupuncture points, which were selected according to traditional Chinese medicine theories, was applied in both groups, while conventional needle acupuncture was applied in treatment group and sham acupuncture (without skin penetration) was applied in control group. Schedule of treatment was the same in both groups, i.e. twice a week for 4 weeks. Key outcome measures were Chalder's Fatigue Scale, the CDC criteria and SF-12 health-related quality of life (HQOL) questionnaire.
Improvements in physical and mental fatigue and HQOL in both groups were observed, but the improvements in treatment group were significantly bigger than in control group (p<0.01 or p<0.05). No adverse events occurred. “Acupuncture is a safe, effective treatment for CFS.”
Wang, T., Zhang, Q., Xue, X and Yeung, A. A systematic review of acupuncture and moxibustion treatment for chronic fatigue syndrome in China. American Journal of Chinese Medicine, 2008, 36, 1, 1-24.
Review of studies but no RCTs.
Bloch, RM and Meggs, WJ. Comorbidity patterns of self-reported chemical sensitivity, allergy, and other medical illnesses with anxiety and depression. Journal of Nutritional & Environmental Medicine, 2007, 16, 2, 136–148.
The relationship of anxiety and depression to chemical sensitivity is controversial. The objective was to assess relationships between self-reported chemical sensitivity, allergy, and medical illnesses to anxiety and depression using a random dialing telephone survey. A community sample in eastern North Carolina representing 1027 households (71% of those contacted) completed the survey. PRIME-MD was used to assess anxiety and depression.
Positive PRIME-MD screens for anxiety was significantly associated with increased risk of reporting chemical sensitivity (OR=2.71). Positive screens for anxiety were similarly associated with allergy (OR=2.08) and with mixed medical illnesses (OR=1.95). Depression was comparable to anxiety in its associations with chemical sensitivity (OR=2.35) and with allergy (OR=2.09), while it was somewhat more related to other illnesses (OR=2.58). Positive responses to the panic question were strongly and equally associated with chemical sensitivity (OR=3.00), with allergy (OR=2.66), and with medical illness (OR=3.25). Logistic regression predicting positive screens for anxiety and for depression showed similar and independent relationships for chemical sensitivity, allergy, and medical illnesses.
The relationship between anxiety and chemical sensitivity is not unique and does not support the contention that chemical sensitivity is somatized anxiety.
Schur, EA., Noonan, C and Buchwald, DS. Prospective study of body mass index, weight change, and fatigue in acute infectious mononucleosis. Journal of Chronic Fatigue Syndrome, 2007, 14, 27-36.
The aim was to examine the influence of body mass index (BMI) and weight change on fatigue severity and failure to recover in individuals with acute infectious mononucleosis.
We prospectively studied 148 individuals presenting with a positive monospot test. We obtained measured weights and vitality subscale scores from the SF-36 at the index visit and at 6 months.
The mean age of the participants was 21 years and 24% were overweight or obese. During acute illness, overweight and obese participants had an adjusted odds ratio for low vitality scores of 2.9 (confidence interval 1.2-7.1) compared to normal weight subjects. Neither index BMI nor 6-month weight gain was significantly associated with prolonged fatigue or failure to recover.
Overweight and obese patients with acute infectious mononucleosis are more likely to experience severe fatigue. In contrast, neither baseline weight nor weight gain appear to impede recovery.
Seishima, M., Mizutani, Y., Shibuya, Y and Arakawa, C. Chronic fatigue syndrome after Human Parvovirus B19 infection without persistent viremia. Dermatology, 2008, 216, 4, 341-346.
It is unclear how often CFS appears after human parvovirus B19 (B19) infection and whether prolonged B19 viremia or some other factors cause CFS. We tried to determine how often CFS appears after B19 infection and whether prolonged B19 DNA presence, antibody production and persistently reduced complement levels occur in CFS patients after B19 infection.
Clinical findings were examined in 210 patients after B19 infection, and CH50, C3 and C4 levels were determined. B19 DNA and antibodies to B19 were also tested in 38 patients' sera including 3 with CFS.
Serum B19 DNA disappeared after 4-5 months in all 18 patients tested. There are no differences in B19 DNA-positive period between patients with and without persistent symptoms. IgM antibody titers to B19 became reduced after 2 months in all 38 patients. Complement levels persistently decreased in a greater proportion of patients with persistent symptoms.
The present study suggests that we should consider the possibility of CFS after B19 infection and that CFS may be derived from several aspects other than prolonged B19 DNA presence in sera.
Watanabe, N., Stewart, R., Jenkins, R., Bhugra, DK and Furukawa, TA. Epidemiology of chronic fatigue, physical illness, and symptoms of common mental disorders: A cross-sectional survey from the second British National Survey of Psychiatric Morbidity. Journal of Psychosomatic Research, 2008, 64, 4, 357-362.
The study aimed to describe the prevalence of chronic fatigue in the general population and to investigate the extent to which its association with physical illness was independent of other symptoms of common mental disorders. Data from the second British National Survey of Psychiatric Morbidity (2000) were analyzed. The survey covered people aged 16 to 74 years living in private households. Chronic fatigue (significant reported fatigue lasting 6 months or more) was ascertained using the revised Clinical Interview Schedule. Information on reported physical illness and sociodemographic factors was considered. Psychiatric symptoms were also assessed using the revised Clinical Interview Schedule.
The prevalence of chronic fatigue was 15.0%, and this showed a significant association with the number of reported physical illnesses (odds ratio [OR] per reported illness, 1.79; 95% confidence interval, 1.68-1.90). It was higher in midlife, in women, in participants with less skilled occupations, and in those with lower educational attainment. Chronic fatigue was strongly associated with the presence of depressive symptoms (OR, 5.37), anxiety-related symptoms (OR, 4.66), and with sleep complaints (OR, 4.41). After adjustment for all socio-demographic and psychiatric factors, the number of reported physical illnesses was less strongly but still significantly associated with chronic fatigue (OR, 1.51; 1.39-1.63).
Physical illness is strongly associated with chronic fatigue. Symptoms of common mental disorders are also associated with chronic fatigue, but the association with physical illness is evident even after adjusting for psychiatric symptoms. The assessment of physically ill people should include chronic fatigue and psychiatric symptoms.
Jenkins, M and Rayman, M. Nutrient intake is unrelated to nutrient status in patients with chronic fatigue syndrome. Journal of Nutritional & Environmental Medicine, 2005, 15, 4, 177–189.
Previous studies on nutrient intake and status in CFS were reviewed. Against this back-ground, we investigated whether low mineral and B vitamin status in patients with CFS was adequately explained by poor nutritional intake. Subsidiary aims were to explore the demographic, dietary, socio-economic, psychological and general health profiles of CFS patients attending our clinics. The sample comprised 51 patients with CFS (CDC criteria ’94) with biomarker values below the laboratory reference range for minerals and B vitamins. Dietary and supplemented nutritional intakes were assessed for comparison with laboratory biomarkers in a hospital outpatient clinic.
Intakes below the UK reference nutrient intake, particularly of Ca and/or vitamin D, I and Se, were common among these patients. There was little correlation between intakes and biomarkers. “These findings may indicate that in some subgroups of CFS patients there is a bias towards a T-helper (Th) 2 type humoral-cytokine expression pattern over a Th1 type cell-mediated (natural killer cell and macrophage activating) immune orientation. An adequate status of many nutrients, including vitamin E and Se, is required for proper immune function. Se deficiency is accompanied by impaired cell-mediated immunity and B-cell function and is also linked to the occurrence, virulence and disease progression of some viral infections... and clinically that low plasma Se is a strong predictor of a poor prognosis in HIV infection. It is quite possible, therefore, that poor Se status may predispose to the progression of post-viral fatigue to CFS... A further concern in relation to low vitamin D intake is that chronic vitamin D deficiency is associated with non-specific bone pain, muscle aches and weakness ...”
Abnormal biomarkers may reflect underlying pathological processes rather than inadequate nutritional intakes and, taken alone, are a poor guide to rational nutritional supplementation. Nevertheless, there appears to be a case for dietary assessment and modest, targeted, vitamin and mineral supplementation in many of these patients.
Chen, R., Moriya, J., Yamakawa, JI., Takahashi, T., Li, Q., Morimoto, S., Iwai, K., Sumino, H., Yamaguchi, N and Kanda, T. Brain atrophy in a murine model of chronic fatigue syndrome and beneficial effect of Hochu-ekki-to (TJ-41). Neurochemical Research, 2008 Mar 4 [Epub ahead of print]. DOI: 10.1007/s11064-008-9620-1.
Dietert, RR and Dietert, JM. Possible role for early-life immune insult including developmental immunotoxicity in chronic fatigue syndrome (CFS) or myalgic encephalomyelitis (ME). Toxicology, 2008 Feb 8 [Epub ahead of print]. DOI:10.1016/j.tox.2008.01.022.
Friedberg, F and Sohl, SJ. Memory for fatigue in chronic fatigue syndrome: The relation between weekly recall and momentary ratings. International Journal of Behavioral Medicine, 2008, 15, 1, 29-33.
Grinde, B. Is chronic fatigue syndrome caused by a rare brain infection of a common, normally benign virus? Medical Hypotheses, 2008 Apr 24 [Epub ahead of print]. DOI:10.1016/j.mehy.2008.03.014
Kishi, A., Struzik, ZR., Natelson, BH., Togo, F and Yamamoto, Y. Dynamics of sleep stage transitions in healthy humans and patients with chronic fatigue syndrome. American Journal of Physiology – Regulatory, Integrative and Comparative Physiology, 2008 Apr 16 [Epub ahead of print].
Nijs, J., Almond, F., De Becker, P., Truijen, S and Paul, L. Can exercise limits prevent post-exertional malaise in chronic fatigue syndrome? An uncontrolled clinical trial. Clinical Rehabilitation, 2008, 22, 5, 426-435.
Stubhaug, B., Atle Lie, S, Ursin, H and Eriksen, HR. Cognitive–behavioural therapy v. mirtazapine for chronic fatigue and neurasthenia: randomised placebo-controlled trial. British Journal of Psychiatry, 2008, 192, 217-223.
Ter Wolbeek, M., van Doornen, LJ., Schedlowski, M., Janssen, OE., Kavelaars, A and Heijnen, CJ. Glucocorticoid sensitivity of immune cells in severely fatigued adolescent girls: A longitudinal study. Psychoneuroendocrinology, 2008, 33, 3, 375-385.
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