ME and CFS References

Myhill, S., Booth, NE and McLaren-Howard, J. Chronic fatigue syndrome and mitochondrial dysfunction. International Journal of Clinical and Experimental Medicine, 2009, 2, 1-16.

This study aims to improve the health of patients suffering from CFS by interventions based on the biochemistry of the illness, specifically the function of mitochondria in producing ATP (adenosine triphosphate), the energy currency for all body functions, and recycling ADP (adenosine diphosphate) to replenish the ATP supply as needed. Patients attending a private medical practice specializing in CFS were diagnosed using the CDC criteria '94.

In consultation with each patient, an integer on the Bell Ability Scale was assigned, and a blood sample was taken for the “ATP profile” test, designed for CFS and other fatigue conditions. Each test produced 5 numerical factors which describe the availability of ATP in neutrophils, the fraction complexed with magnesium, the efficiency of oxidative phosphorylation, and the transfer efficiencies of ADP into the mitochondria and ATP into the cytosol where the energy is used. With the consent of each of 71 patients and 53 normal, healthy controls, the 5 factors have been collated and compared with the Bell Ability Scale.

The individual numerical factors show that patients have different combinations of biochemical lesions. When the factors are combined, a remarkable correlation is observed between the degree of mitochondrial dysfunction and the severity of illness (p<0.001). Only 1 of the 71 patients overlaps the normal region.

The “ATP profile” test is a powerful diagnostic tool and can differentiate patients who have fatigue and other symptoms as a result of energy wastage by stress and psychological factors from those who have insufficient energy due to cellular respiration dysfunction. The individual factors indicate which remedial actions, in the form of dietary supplements, drugs and detoxification, are most likely to be of benefit, and what further tests should be carried out.

PSYCHOLOGY AND PSYCHIATRY

Chew-Graham, CA., Dixon, R., Shaw, JW., Smyth, N., Lovell, K and Peters, S. Practice nurses' views of their role in the management of chronic fatigue syndrome/myalgic encephalitis: a qualitative study. BMC Nursing, 2009, 8:2. DOI:10.1186/1472-6955-8-2.

The NICE guidelines suggest that patients with CFS/Myalgic Encephalitis (CFS/ME) should be managed in Primary Care. Practice Nurses are increasingly being involved in the management of long-term conditions, so are likely to also have a growing role in managing CFS/ME. [E in ME refers to encephalomyelitis, see ICD-10 G93.3, Ed.] However their attitudes to, and experiences of patients with CFS/ME and its management must be explored to understand what barriers may exist in developing their role for this group of patients. The aim of this study was to explore Practice Nurses' understanding and beliefs about CFS/ME and its management. Semi-structured interviews with 29 Practice Nurses were transcribed verbatim.

Practice nurses had limited understanding of CFS/ME which had been largely gained through contact with patients, friends, personal experiences and the media rather than formal training. They had difficulty seeing CFS/ME as a long term condition. They did identify a potential role they could have in management of CFS/ME but devalued their own skills in psychological intervention, and suggested counselling as an appropriate therapeutic option. They recognised a need for further training and ongoing supervision from both medical and psychological colleagues. Some viewed the condition as contentious and held pejorative views about CFS/ME. Such scepticism and negative attitudes will be a significant barrier to the management of patients with CFS/ME in primary care.

The current role of Practice Nurses in the ongoing management of patients with CFS/ME is limited. Practice Nurses have little understanding of the evidence-base for treatment of CFS/ME, particularly psychological therapies, describing management options in terms of advice giving, self-help or counselling. Practice Nurses largely welcomed the potential development of their role in this area, but identified barriers and training needs which must be addressed to enable them to feel confident managing of patients with this condition. Training must begin by addressing negative attitudes to patients with CFS/ME.

http://www.biomedcentral.com/1472-6955/8/2

Goudsmit, EM., Stouten, B and Howes, S. Illness intrusiveness in myalgic encephalomyelitis. An exploratory study. Journal of Health Psychology, 2009, 14, 2, 215-221.

This study assessed the relationship between illness intrusiveness, symptoms, disability and depression in patients with myalgic encephalomyelitis (ME). Participants were 16 patients with ME (criteria based on Ramsay's description) and 8 patients with ME plus co-morbid disorders.

The patients with co-morbid disorders reported greater illness intrusiveness than the patients with ME alone, but there were no differences between the groups on the other variables. Significant correlations were found between illness intrusiveness on the one hand, and fatigue, cognitive dysfunction, disability and depression, on the other. We conclude that ME is a disabling illness which has a major impact on various life domains.

[Ed. Note: The mean IIRS score for the total sample was 66.30. For the subset with co-morbid disorders, the mean was 72. The scores for ME are similar to those reported by Dancey and Friend who studied CFS, but exceed the means documented for various forms of cancer, MS and end-stage renal disease.

A longer article describing the concept of illness intrusiveness in detail, plus the normative data for various conditions, can be found in the section 'ME Research Online' at http://freespace.virgin.net/david.axford/melist.htm]

Heim, C., Nater, UM., Maloney, E., Boneva, R., Jones, JF and Reeves, WC. Childhood trauma and risk for chronic fatigue syndrome. Association with neuroendocrine dysfunction. Archives of General Psychiatry, 2009, 66, 1, 72-80.

Childhood trauma appears to be a potent risk factor for CFS. Evidence from developmental neuroscience suggests that early experience programs the development of regulatory systems that are implicated in the pathophysiology of CFS, including the hypothalamic-pituitary-adrenal (HPA) axis. However, the contribution of childhood trauma to neuroendocrine dysfunction in CFS remains obscure.

The aim of the study was to replicate findings on the relationship between childhood trauma and risk for CFS and to evaluate the association between childhood trauma and neuroendocrine dysfunction in CFS. Sample; a case-control study of 113 persons with CFS (CDC criteria '94, operationalised) and 124 well control subjects identified from a general population sample of 19 381 adult residents of Georgia.

Main outcome measures included self-reported childhood trauma (sexual, physical, and emotional abuse; emotional and physical neglect), psychopathology (depression, anxiety, and posttraumatic stress disorder), and salivary cortisol response to awakening.

Individuals with CFS reported significantly higher levels of childhood trauma and psycho-pathological symptoms than control subjects. Exposure to childhood trauma was associated with a 6-fold increased risk of CFS. Sexual abuse, emotional abuse, and emotional
neglect were most effective in discriminating CFS cases from controls. There was a graded relationship between exposure level and CFS risk. The risk of CFS conveyed by childhood trauma further increased with the presence of posttraumatic stress disorder symptoms. Only individuals with CFS and with childhood trauma exposure, but not individuals with CFS without exposure, exhibited decreased salivary cortisol concentrations after awakening compared with control subjects.

Our results confirm childhood trauma as an important risk factor of CFS. In addition, neuroendocrine dysfunction, a hallmark feature of CFS, appears to be associated with childhood trauma. This possibly reflects a biological correlate of vulnerability due to early developmental insults. Our findings are critical to inform pathophysiological research and to devise targets for the prevention of CFS.

[Ed. Note: The results could reflect the heterogeneity of the population and the fact that the criteria are not able to differentiate between CFS as originally conceptualized, and the effects of chronic stress.]

Johnson, SK., Gil-Rivas, V and Schmaling, KB. Coping strategies in chronic fatigue syndrome: outcomes over time. Stress and Health, 2008, 24, 305-312.

This paper examined the contribution of coping strategies and neuroticism to longitudinal outcomes in a tertiary care sample of participants with CFS). Coping strategies and neuroticism were assessed among 93 participants with CFS (CDC criteria '94), and used to predict participants' illness-related outcomes.

Coping by instrumental support was the only strategy associated with clinical outcomes over time: more reliance on instrumental support predicted less vitality over time after accounting for the level of vitality at the index visit. Neuroticism and coping strategies were not associated with fatigue symptoms, physical functioning or role functioning over time.

http://www3.interscience.wiley.com/journal/119338876/abstract

Goudsmit, EM, Shepherd, C., Dancey, CP and Howes, S. ME: Chronic fatigue syndrome or a distinct clinical entity? Health Psychology Update, 2009, 18, 1, 26-33.

Myalgic encephalomyelitis (ME) is a disabling condition characterised by profound fatigue following minimal exertion and a delay in recovery after exertion ends. In 1988, when specialists introduced the concept of CFS, it was assumed that the illness in question was identical to ME but the lack of research criteria for the latter has prevented the testing of this assumption.

In this article, we propose criteria and guidelines which can be used to study ME and determine whether it is a synonym for CFS or one of several subgroups contained within the CFS construct. If clinically meaningful differences are identified, the criteria may help to increase diagnostic precision and facilitate further research into the cause, course and treatment of ME.

Jason, LA., Najar, N., Porter, N and Reh, C. Evaluating the Centers for Disease Control's empirical chronic fatigue syndrome case definition. Journal of Disability Policy Studies, 2009, in press. DOI: 10.1177/1044207308325995.

The Centers for Disease Control and Prevention (CDC) recently developed an empirical case definition that specifies criteria and instruments to diagnose CFS in order to bring more methodological rigor to the current CFS case definition. The present study investigated this new definition with 27 participants with a diagnosis of CFS (CDC criteria '94) and 37 participants with a diagnosis of a Major Depressive Disorder. Participants completed questionnaires measuring disability, fatigue, and symptoms.

Findings indicated that 38% of those with a diagnosis of a Major Depressive Disorder were misclassified as having CFS using the new (2005) CDC definition. Given the CDC’s stature and respect in the scientific world, this new definition might be widely used by investigators and clinicians. This might result in the erroneous inclusion of people with primary psychiatric conditions in CFS samples, with detrimental consequences for the interpretation of epidemiologic, etiologic, and treatment efficacy findings for people with CFS.

THERAPEUTICS

Friedberg, F and Sohl, S. Cognitive-behavior therapy in chronic fatigue syndrome: is improvement related to increased physical activity? Journal of Clinical Psychology, 2009, 65, 4, 423-442.

This multiple case study of cognitive-behavioral treatment (CBT) for CFS compared self-report and behavioral outcomes. Eleven relatively high-functioning participants (out of a group of 17) with CFS (CDC criteria '94) received 6-32 sessions of outpatient graded-activity oriented CBT. Self-report outcomes included measures of fatigue impact, physical function, depression, anxiety, and global change. Behavioral outcomes included actigraphy and the 6-minute walking test.

Global change ratings were very much improved (n=2), much improved (n=2), improved (n=5), and no change (n=2). Of those reporting improvement, clinically significant actigraphy increases (n=3) and decreases (n=4) were found, as well as no significant change (n=2). Effect sizes (Cohen's d) were moderate for fatigue impact (-.78), small for physical functioning as measured by the MOS (.35), anxiety and depression and near zero for the 6-minute walking test. It was also small for activity levels as measured by actigraphy (-.13)*. The number of visits did not significantly predict any outcome variable.

The nature of clinical improvement in CBT trials for high-functioning CFS patients may be more ambiguous than that postulated by the cognitive-behavioral model.

Extracts from discussion: "Furthermore, if clinically significant improvement is defined by achieving normal population values (Jacobsen & Truax, 1991), then no participant reached this level on the fatigue severity scale (Krupp et al., 1989) and only two participants met population values on the SF-36PF subscale (Ware, Snow, Kosinski, & Gandek, 2000). This is consistent with successful CBT studies that, despite clinical improvements, have not yielded outcomes equivalent to recovery or cure in both short- (e.g., Prins et al., 2001) and long-term (e.g., Deale, Husain, Chalder, & Wessely, 2001) follow-ups... Although cognitive-behavioral theory predicts improved well-being and functioning via cognitively-mediated increases in activity (e.g., Bleijenberg, Prins, & Bazelmans, 2003; Butler et al., 1991; Prins & Bleijenberg, 1999; Surawy et al., 1995), the clinical trial outcomes in support of the theory were conducted on largely low-functioning, unemployed participants, many of whom were receiving disability benefits (Ross et al., 2004). The current study, conducted on mostly employed participants, calls into question whether real-time behavioral change is associated with such improvement in this subgroup... Given that 7 of 11 participants were employed at baseline and performed many non-work activities, it may be unrealistic to expect that CBT will substantially increase physical and role functioning and, by implication, real-time physical activity and exercise tolerance in these high-functioning individuals (Friedberg & Krupp, 1994). By comparison, the lower functioning participants in previous clinical trials may have been more likely to show measurable increases in physical and role activity as a result of CBT (Friedberg, 1999)... Although our participants may have been mobilized by their graded activity assignments in the initial phase of treatment, the effect of this low-level activity (sometimes in combination with other CBT strategies, e.g., relaxation, sleep scheduling) may have been to facilitate a healthier balance among activity, rest, and leisure (Friedberg, 2006) that in only some cases yielded greater overall activity levels. Thus, assigned increases in physical activity may be important to the process of therapeutic behavioral change, but improved outcomes may not require net increases in overall physical activity especially in already high-functioning participants... This uncontrolled small sample CBT study in individuals with CFS found that improvements were strongest for self-report fatigue impact. However, treatment gains may be attributable to nonspecific effects such as therapist attention or passage of time, rather than the targeted intervention. Although conclusions about cause and effect cannot be made, this study revealed an ambiguous picture of clinical outcomes in relatively high-functioning CFS patients that has not been previously reported."

[Ed. Note: *For other d values related to CBT and graded activity, see Malouff et al 2008 and Nezu et al 2001). The drop-out rate was 35.3%.]

http://www3.interscience.wiley.com/journal/122197496/abstract

REVIEWS

Christopher, G and Thomas, M. Social problem solving in chronic fatigue syndrome: preliminary findings. Stress and Health, 2009. Online Oct. 16th. DOI:10.1002/smi.1233.

This paper investigates social problem solving in CFS, a condition characterized by reduced activity levels and excessive mental fatigue. Although intra- and inter-personal problems are prevalent, no studies have explored social problem-solving skills in this group. Patients with CFS (CDC criteria '94) from the MCT study were split into two groups: those with either high (n=10) or low (n=11) alexithymia, a condition associated with affect dysregulation.

The high alexithymic group viewed problems as threatening, responding either impulsively or avoiding responding altogether; they were poor also in the use of compensatory strategies, which, taken together, increases the likelihood of a negative outcome from attempts at conflict resolution. These findings go some way in successfully identifying potential subgroupings in CFS sufferers and has important implications in terms of the therapy offered.

http://www3.interscience.wiley.com/journal/108567449/issue

Clark, LV and White, PD. Chronic fatigue syndrome. Journal of Rehabilitation Medicine, 2008, 40, 882-883.

Letter challenging view that GET has adverse effects.

In response, Nijs, Paul and Wallman (ibid, 883-4) note that the apparent need to reduce activity levels under certain circumstances acknowledges that there are problems. The letter also challenges comments relating to effect on immune system, noting that studies did not assess same markers, hence inconsistent findings.

[Ed. Note: Adverse effects may not only be due to inexperienced therapists, as claimed. The Belgian audit indicated adverse effects after treatment from qualified specialists in centers focused on treating CFS. Evidence of effect size suggests small to modest effects (e.g. Malouff et al 2008). The alleged lack of adverse effects may reflect the inadequacy of measures. When objective measures are used to assess activity levels, only one study revealed increases in activity, e.g. Friedberg and Sohl. See also Black and McCully. White and colleagues have not provided objective evidence of increases in activity following GET, or improvements in immune function, antibody titers where appropriate, e.g. Chia and Chia 2005. White's own study (JCFS) found abnormal immune response after minimal exertion. See paper on pacing by Goudsmit and Howes, HPU, 2008]

Dickson, A., Toft, A and O'Carroll, RE. Neuropsychological functioning, illness perception, mood and quality of life in chronic fatigue syndrome, autoimmune thyroid disease and healthy participants. Psychological Medicine, 2009 Jan 15. [E-pub]

DOI:10.1017/S0033291708004960.

This study attempted to longitudinally investigate neuropsychological function, illness representations, self-esteem, mood and quality of life (QoL) in individuals with CFS and compared them with both healthy participants and a clinical comparison group of individuals with autoimmune thyroid disease (AITD).

Neuropsychological evaluation was administered at two time points, five weeks apart. Twenty-one individuals with CFS (CDC criteria '94), 20 individuals with AITD and 21 healthy participants were matched for age, pre-morbid intelligence, education level and socio-economic status (SES). All groups also completed measures of illness perceptions, mood, self-esteem and QoL at both time points.

The CFS group showed significantly greater impairment on measures of immediate and delayed memory, attention and visuo-constructional ability, and reported significantly higher
levels of anxiety and depression. After controlling for the effects of mood, the CFS group still demonstrated significant impairment in attention. The CFS group also reported significantly lower self-reported QoL than the AITD and healthy participants. In terms of illness perceptions, the AITD group believed that their condition would last longer, that they had more treatment control over their condition, and reported less concern than the CFS group.

These results suggest that the primary cognitive impairment in CFS is attention and that this is not secondary to affective status. The lower treatment control perceptions and greater illness concerns that CFS patients report may be causally related to their affective status.

Goedendorp, MM., Knoop H, Schippers, GM and Bleijenberg, G. The lifestyle of patients with chronic fatigue syndrome and the effect on fatigue and functional impairments. Journal of Human Nutrition and Dietetics, 2009 Feb 13.

[E-pub]. DOI: 10.1111/j.1365-277X.2008.00933.x

Little is known about the lifestyle of patients with CFS and its influence on symptoms of CFS. The present study aimed to investigate the lifestyle of patients with CFS, and to assess whether lifestyle factors are related to fatigue and functional impairments.

Two hundred and forty-seven patients fulfilling the CDC criteria ('94 and '05) for CFS were included. Validated questionnaires were used to collect data on lifestyle factors, smoking, intake of alcohol, fat, fibres, fruit and vegetables, body mass index (BMI), fatigue severity and functional impairments.

Of the CFS patients, 23% smoked, 32% had an unhealthy BMI, and none had an unhealthy alcohol intake. A majority had an unhealthy food intake: 70% had unhealthy fat, fruit and vegetable intake, and 95% had unhealthy fibre intake. Compared with the general Dutch population, significantly fewer CFS patients were overweight. Significantly more female CFS

patients abstained from alcohol, and fewer male CFS patients smoked. Unhealthy lifestyle factors were not significantly associated with fatigue severity or functional impairments.

"CFS patients tend to lead a healthier lifestyle compared to the general Dutch population. However, no relationship was found between lifestyle factors and fatigue severity and functional impairments in CFS."

Gupta, A., Vij, G., Sharma, S., Tirkey, N., Rishi, P and Chopra, K. Curcumin, a polyphenolic antioxidant, attenuates chronic fatigue syndrome in murine water immersion stress model. Immunobiology, 2009, 214, 33-39.

[Ed. Note: This study employed a murine model. Given the limitations of the model, the findings may not be applicable to humans with CFS. Moreover, there is no reason why curcumin should not have been tested in humans.]

Hughes, JL. Chronic fatigue syndrome and occupational disruption in primary care: is there a role for occupational therapy? Journal of Occupational Therapy, 2009, 72, 1, 2-10.

This paper presents the findings of a postal survey that examined the experience of CFS/ME in the primary care setting. The views of 51 general practitioners (GPs) (response rate of 30%) and 51 people that had experienced CFS/ME (response rate of 61%) were collected in an attempt to describe both the occupational disruption experienced due to CFS/ME and the current management offered in primary care, and to investigate whether there was an early intervention role for occupational therapy.

The greatest level of occupational disruption reported was in the performance of self-care and productivity tasks and the most helpful intervention reported was that of acknowledgement of the condition and its implications. The GPs rated the use of CBT and graded exercise therapy as more beneficial than medical care for CFS/ME and many offered advice on these interventions, but 57% of people with CFS/ME reported that they had received unhelpful advice and/or treatment from their GP.

Currently, there is little research evidence to support any particular interventions for people with CFS/ME in primary care and the prevention of occupational dysfunction, as often seen in secondary and tertiary care, is a role that could be fulfilled by occupational therapists.

[Ed. Note: the main interventions offered by GPs were taking time off work, graded exercise, and antidepressants. Only 27% offered CBT. The patient sample was not diagnosed using specified criteria e.g. CDC.]

Lerner, AM., Beqaj, SH and Fitzgerald, JT. Validation of the energy index point score to serially measure the degree of disability in patients with chronic fatigue syndrome. In Vivo, 2008, 22, 6, 799-801.

A simple quantitative accurate method for assessing the degree of fatigue in patients with CFS is necessary for physicians and patients. Severity of the disease and recovery can, thus, be assayed.

From February 1-27, 2007, fifty-six consecutive CFS patients at a single treatment center were simultaneously evaluated by the patient with the fatigue severity score (FSS), and by consensus of both patient and physician by the energy index (EI) point score. The FSS and EI correlated well, 0.67, p<0.001. The El point score is a validated reliable method to assess fatigue in CFS patients

Lin, J-MS., Brimmer, DJ., Boneva, RS., Jones, JF and Reeves, WC. Barriers to healthcare utilization in fatiguing illness: a population-based study in Georgia. BMC Health Services Research, 2009, 9:13. DOI:10.1186/1472-6963-9-13.

Maes, M and Leunis, JC. Normalization of leaky gut in chronic fatigue syndrome (CFS) is accompanied by a clinical improvement: effects of age, duration of illness and the translocation of LPS from gram-negative bacteria. NeuroEndocrinology Letters, 2008, 29, 6, 902-910.

There is now evidence that an increased translocation of LPS from gram negative bacteria with subsequent gut-derived inflammation, i.e. induction of systemic inflammation and oxi-dative & nitrosative stress (IO&NS), is a new pathway in CFS. The present study examines the serum concentrations of IgA and IgM to LPS of gram-negative enterobacteria, i.e. Hafnia Alvei; Pseudomonas Aeruginosa, Morganella Morganii, Pseudomonas Putida, Citrobacter Koseri, and Klebsielle Pneumoniae in CFS patients both before and after intake of natural anti-inflammatory and anti-oxidative substances (NAIOSs), such as glutamine, N-acetyl cysteine and zinc, in conjunction with a leaky gut diet during 10-14 months. We measured the above immune variables as well as the Fibromyalgia and Chronic Fatigue Syndrome Rating Scale in 41 patients with CFS before and 10-14 months after intake of NAIOSs.

Subchronic intake of those NAIOSs significantly attenuates the initially increased IgA and IgM responses to LPS of gram negative bacteria. Up to 24 patients showed a significant clinical improvement or remission 10-14 months after intake of NAIOSs. A good clinical
response is significantly predicted by attenuated IgA and IgM responses to LPS, the younger age of the patients, and a shorter duration of illness (<5 years).

The results show that normalization of the IgA and IgM responses to translocated LPS may predict clinical outcome in CFS. The results support the view that a weakened tight junction barrier with subsequent gut-derived inflammation is a novel pathway in CFS and that it is a new target for drug development in CFS. Meanwhile, CFS patients with leaky gut can be treated with specific NAIOSs and a leaky gut diet.

Maes, M. Inflammatory and oxidative and nitrosative stress pathways underpinning chronic fatigue, somatization and psychosomatic symptoms. Current Opinion in Psychiatry, 2009, 22, 1, 75-83.

The aim of this paper is to review recent findings on inflammatory and oxidative and nitrosative stress (IO&NS) pathways in chronic fatigue and somatization disorder.
Activation of IO&NS pathways is the key phenomenon underpinning CFS: intracellular
inflammation, with an increased production of nuclear factor kappa beta, cyclo-oxygenase-2 (COX-2) and inducible NO synthase (iNOS); and damage caused by O&NS to membrane fatty acids and functional proteins. These IO&NS pathways are induced by a number of trigger factors, for example psychological stress, strenuous exercise, viral infections and an increased translocation of LPS from gram-bacteria (leaky gut). The 'psychosomatic' symptoms experienced by CFS patients are caused by intracellular inflammation (aches and pain, muscular tension, fatigue, irritability, sadness, and the subjective feeling of infection); damage caused by O&NS (aches and pain, muscular tension and fatigue); and gut-derived inflammation (complaints of irritable bowel). Inflammatory pathways (monocytic activation) are also detected in somatizing disorder.

'Functional' symptoms, as occurring in CFS and somatization, have a genuine organic cause, that is activation of peripheral and central IO&NS pathways and gut-derived inflammation. The development of new drugs, aimed at treating those disorders, should target these
IO&NS pathways.

Raison, C.L., Lin, J.S and Reeves, W.C. Association of peripheral inflammatory markers with chronic fatigue in a population-based sample, Brain, Behavior, and Immunity, 2009, 23, 3, 327-337.

The combined inflammation factor was increased in both CFS and ISF. Subjects with CFS and ISF did not differ on any of the inflammation measures. In the entire subject population, the physical component summary score (PCS), but not the mental component summary score (MCS), from the Medical Outcomes Study Short Form-36 (SF-36) was negatively associated with each of the inflammation measures. Depressive symptoms were also associated with increased log hs-CRP. After adjustment for age, sex, race, location of residence, BMI, depressive status and immune modulating medications, subjects classified as ISF continued to demonstrate increased log hs-CRP, WBC and elevations on the inflammation factor when compared to well controls; however, associations between CFS and log hs-CRP and the inflammation factor were no longer statistically significant. After adjustment, PCS score also remained independently associated each of the inflammation measures. These findings support a role for innate immune activation in unexplained fatigue and unwellness, but do not suggest that immune activation is specific to CFS.

Sakudo, A., Kuratsune, H., Kato, YH and Ikuta K. Secondary structural changes of proteins in fingernails of chronic fatigue syndrome patients from Fourier-transform infrared spectra. Clinica Chimica Acta, 2009, 402, 1-1, 75-78.

Generally, nails can be an index of health, with abnormalities sometimes found under diseased conditions. Fatigue is also supposed to affect the condition of nails. Possible differences in infrared (IR) spectra of nail plates of 65 CFS patients (CDC criteria '94) compared to 41 healthy control subjects were investigated in this study.

Using an attenuated total reflection (ATR)-Fourier-transform infrared (FTIR) spectrophotometer, spectra in the region of 4000-600/cm were obtained. The amide I region was then separated by Fourier deconvolution and curve fitting based on the Gauss and Lorentz formula and revealed differences in the secondary structural content of proteins compared to healthy donors.

The specific secondary structural pattern commonly observed in nails of male and female CFS patients in the absence and presence of medication indicated a decreased alpha-helix content and increased beta-sheet content, suggesting reduced levels of normal elements of the nail plate.

This provides the first evidence of alterations in the fingernails of CFS patients which could be detected by IR spectroscopy. Possible explanations for the alterations will be discussed.

Sakudo, A., Kato, YH., Tajima, S., Kuratsune, H and Ikuta, K. Visible and near-infrared spectral changes in the thumb of patients with chronic fatigue syndrome. Clinica Chimica Acta, 2009 Feb 24. [Epub ahead of print]

CFS patients show a persistent fatigue condition with muscle pain and impairment of concentration, memory, and sleep. Presently, the physiological basis of CFS remains unclear. In this study, spectroscopic differences in the thumb were compared between 103 CFS patients (CDC criteria '94) and 122 healthy controls to examine possible changes of levels of oxygenated or deoxygenated hemoglobin.

Visible and near-infrared (Vis-NIR) spectroscopy was used to examine possible changes in the region of 600-1100 nm.

Vis-NIR spectra showed sharp peaks at 694, 970 and 1060 nm and broad peaks in the regions of 740-760 and 830-850 nm. As these peaks are possibly related to oxyhemoglobin, cytochrome c oxidase and water, levels of these factors were compared between the two groups.

Statistical analysis of the absorbance of Vis-NIR spectra showed a significant decrease in water content, a significant increase in oxyhemoglobin content, and a significant increase in the oxidation of heme a+a(3) and copper in cytochrome c oxidase in CFS patients. These changes imply accelerated blood flow and energy metabolism in the thumbs of CFS patients.

Sullivan, Å., Nord, CE and Evengård, B. Effect of supplement with lactic-acid producing bacteria on fatigue and physical activity in patients with chronic fatigue syndrome. Nutrition Journal, 2009, 8:4. DOI: 10.1186/1475-2891-8-4.

Disturbances in intestinal microbial ecology and in the immune system of the host have been implicated as a part of the pathogenesis in CFS. Probiotic lactic acid producing bacteria have been shown to prevent and alleviate gastrointestinal disturbances and to normalize the cytokine profile which might be of an advantage for patients suffering from CFS. The aim of the study was to evaluate the effect of Lactobacillus paracasei ssp. Paracasei F19, Lactobacillus acidophilus NCFB 1748 and Bifidobacterium lactis Bb12 on fatigue and physical activity in CFS patients. Fifteen patients fulfilling the CDC criteria '94 were included in the study. The patients had high fatigue severity scores and high disability scores.

During the first two weeks baseline observations without treatment were assessed, succeeded by four weeks of intake of a probiotic product and a four-week follow-up period. The fatigue, health and physical activity was assessed by the use of the Visual Analogue Scales and the SF-12 Health Survey. Faecal samples were collected and the normal microflora was analysed.

Neurocognitive functions improved during the study period while there were no significant changes in fatigue and physical activity scores. No major changes occurred in the gastro-intestinal microflora. At the end of the study 6 of 15 patients reported that they had improved according to the assessment described. The findings in this study that improvement of health is possible to achieve should encourage further studies with interventions with probiotics in patients with CFS.

http://www.nutritionj.com/content/pdf/1475-2891-8-4.pdf

Thomas, MA., Sadlier, MJ and Smith, AP. A multiconvergent approach to the rehabilitation of patients with chronic fatigue syndrome: a comparative study. Physiotherapy, 2008, 94, 35-42.

This study investigated the efficacy of a rehabilitation technique for the treatment of CFS that was developed by a physiotherapist. Data collected retrospectively from a pilot study indicated that patients benefited from this multiconvergent approach, so further assessments were warranted. Treatment efficacy was assessed by comparing the primary and secondary outcome measures of patients attending multiconvergent therapy (MCT) with those of patients attending relaxation therapy and a group of non-intervention controls. The active treatment took place at a clinic within the physiotherapy outpatient unit. Relaxation therapy and all assessments were conducted at the psychology unit. Thirty-five participants with CFS (CDC criteria '94) were recruited from two outpatient clinics and an existing patient panel. Patients were assigned to either MCT (n = 12) or relaxation therapy (n = 14). Nine participants who received general medical care were used as a comparison group. The Karnofsky performance scale was used as the primary outcome measure of function. Secondary outcome measures assessing overall improvement in patient condition, fatigue and disability levels were also administered.

A significant percentage of the patients attending the MCT sessions showed improvement in the primary outcome score used to measure the success of the treatment (MCT = 83%, relaxation = 21%, controls = 0; p<0.001). A significant percentage of this group also reported improvement in their overall condition (MCT = 92%, relaxation = 64%, controls = 22%; p<0.001), lower fatigue levels (MCT = 83%, relaxation = 57%, controls = 11%; p<0.001) and lower levels of disability (MCT = 75%, relaxation = 43%, controls = 11%; p=0.032) immediately post-therapy. In addition, these improvements were maintained at 6-month follow-up.

Outcomes from this small preliminary study were encouraging. The multiconvergent approach produced significant improvements for standardised primary and secondary outcome measures. Further research is required to examine the efficacy of this approach over time, and its effectiveness on a larger scale within the primary healthcare setting using additional therapists trained in the technique.

Van Houdenhove., Van Den Eede, F and Luyten, P. Does hypothalamic–pituitary–adrenal axis hypofunction in chronic fatigue syndrome reflect a ‘crash’ in the stress system? Medical Hypotheses, 2009 in press. DOI:10.1016/j.mehy.2008.11.044.

Wyller, VB., Eriksen, HR and Malterud, K. Can sustained arousal explain the chronic fatigue syndrome? Behavioral and Brain Functions, 2009, 5:10. DOI:10.1186/1744-9081-5-10.

We present an integrative model of disease mechanisms in the CFS, unifying empirical findings from different research traditions. Based upon the Cognitive activation theory of stress (CATS), we argue that new data on cardiovascular and thermoregulatory regulation indicate a state of permanent arousal responses - sustained arousal - in this condition. We suggest that sustained arousal can originate from different precipitating factors (infections, psychosocial challenges) interacting with predisposing factors (genetic traits, personality) and learned expectancies (classical and operant conditioning). Furthermore, sustained arousal may explain documented alterations by establishing vicious circles within immunology (Th2 (humoral) vs Th1 (cellular) predominance), endocrinology (attenuated HPA axis), skeletal muscle function (attenuated cortical activation, increased oxidative stress) and cognition (impaired memory and information processing). Finally, we propose a causal link between sustained arousal and the experience of fatigue. The model of sustained arousal embraces all main findings concerning CFS disease mechanisms within one theoretical framework.

http://www.behavioralandbrainfunctions.com/content/pdf/1744-9081-5-10.pdf

Kumar, A and Garg, R. Protective effects of antidepressants against chronic fatigue syndrome – induced behavioral changes and biochemical alterations. Fundamental & Clinical Pharmacology, 2009, Jan 10 [E pub]. DOI: 10.1111/j.1472-8206.2008.00638.x

[Ed. Note: This study involved mice and found that certain drugs protected them from the adverse reactions from seven days of forced swimming.]

Mastropasqua, L et al. Ocular manifestations in chronic fatigue syndrome. Annals of Opthalmology, 2000, 32, 3, 219-224.

Study of 37 patients with CFS which identified ocular abnormalities which are difficult to explain in terms of the CBT model, e.g. tear film deficiency, increase in near exophoria, and abnormal fusional vergeance and convergence. The authors link changes to a defect in oxidative metabolism with resulting acceleration of glycosis in the working skeletal muscles.

COMPLETE REFERENCES FOR SIGNIFICANT E-PUBS

Mathew, SJ., Mao, X., Keegan, KA., Levine, SM., Smith, EL., Heier, LA., Otcheretko, V., Coplan, J and Shungu DC. Ventricular cerebrospinal fluid lactate is increased in chronic fatigue syndrome compared with generalized anxiety disorder: an in vivo 3.0 T 1H MRS imaging study. NMR in Biomedicine, 2008, 22, 3, 251-258.