The influence of aerobic fitness and fibromyalgia on cardiorespiratory and perceptual responses to exercise in patients with chronic fatigue syndrome

Abstract:

OBJECTIVE: To investigate cardiorespiratory and perceptual responses to exercise in patients with chronic fatigue syndrome (CFS), accounting for comorbid fibromyalgia (FM) and controlling for aerobic fitness.

METHODS: Twenty-nine patients with CFS only, 23 patients with CFS plus FM, and 32 controls completed an incremental bicycle test to exhaustion. Cardiorespiratory and perceptual responses were measured. Results were determined for the entire sample and for 18 subjects from each group matched for peak oxygen consumption.

RESULTS: In the overall sample, there were no significant differences in cardiorespiratory parameters between the CFS only group and the controls. However, the CFS plus FM group exhibited lower ventilation, lower end-tidal CO2, and higher ventilatory equivalent of carbon dioxide compared with controls, and slower increases in heart rate compared with both patients with CFS only and controls. Peak oxygen consumption, ventilation, and workload were lower in the CFS plus FM group. Subjects in both the CFS only group and the CFS plus FM group rated exercise as more effortful than did controls. Patients with CFS plus FM rated exercise as significantly more painful than did patients with CFS only or controls. In the subgroups matched for aerobic fitness, there were no significant differences among the groups for any measured cardiorespiratory response, but perceptual differences in the CFS plus FM group remained.

CONCLUSION: With matching for aerobic fitness, cardiorespiratory responses to exercise in patients with CFS only and CFS plus FM are not different from those in sedentary healthy subjects. While CFS patients with comorbid FM perceive exercise as more effortful and painful than do controls, those with CFS alone do not. These results suggest that aerobic fitness and a concurrent diagnosis of FM are likely explanations for currently conflicting data and challenge ideas implicating metabolic disease in the pathogenesis of CFS.

 

Source: Cook DB, Nagelkirk PR, Poluri A, Mores J, Natelson BH. The influence of aerobic fitness and fibromyalgia on cardiorespiratory and perceptual responses to exercise in patients with chronic fatigue syndrome. Arthritis Rheum. 2006 Oct;54(10):3351-62. https://www.ncbi.nlm.nih.gov/pubmed/17009309

 

Increased serum IgA and IgM against LPS of enterobacteria in chronic fatigue syndrome (CFS): indication for the involvement of gram-negative enterobacteria in the etiology of CFS and for the presence of an increased gut-intestinal permeability

Abstract:

There is now evidence that chronic fatigue syndrome (CFS) is accompanied by immune disorders and by increased oxidative stress. The present study has been designed in order to examine the serum concentrations of IgA and IgM to LPS of gram-negative enterobacteria, i.e. Hafnia alvei; Pseudomonas aeruginosa, Morganella morganii, Proteus mirabilis, Pseudomonas putida, Citrobacter koseri, and Klebsiella pneumoniae in CFS patients, patients with partial CFS and normal controls.

We found that the prevalences and median values for serum IgA against the LPS of enterobacteria are significantly greater in patients with CFS than in normal volunteers and patients with partial CFS. Serum IgA levels were significantly correlated to the severity of illness, as measured by the FibroFatigue scale and to symptoms, such as irritable bowel, muscular tension, fatigue, concentration difficulties, and failing memory.

The results show that enterobacteria are involved in the etiology of CFS and that an increased gut-intestinal permeability has caused an immune response to the LPS of gram-negative enterobacteria. It is suggested that all patients with CFS should be checked by means of the IgA panel used in the present study and accordingly should be treated for increased gut permeability.

 

Source: Maes M, Mihaylova I, Leunis JC. Increased serum IgA and IgM against LPS of enterobacteria in chronic fatigue syndrome (CFS): indication for the involvement of gram-negative enterobacteria in the etiology of CFS and for the presence of an increased gut-intestinal permeability. J Affect Disord. 2007 Apr;99(1-3):237-40. Epub 2006 Sep 27. https://www.ncbi.nlm.nih.gov/pubmed/17007934

 

An investigation of the long-term benefits of antidepressant medication in the recovery of patients with chronic fatigue syndrome

Abstract:

Two hundred and seventy-five patients fulfilling the Centre for Disease Control (CDC) criteria for Chronic Fatigue Syndrome (CFS) completed measures assessing illness history, global ratings of well being, sleep, activity and psychopathology at baseline, 6 months, 18 months and 3 year follow-up. Forty-nine of these patients had been prescribed antidepressant medication, namely Tricyclic drugs or Selective Serotonin Re-uptake Inhibitors (SSRI).

Data from the current study suggests that patients in the antidepressant medication group recover at a faster rate over time when compared to the untreated patient sample. In addition, the positive effects of antidepressant therapy are maintained at the 3-year follow-up point. It appears from these data that the SSRI in particular are responsible for improvements in the condition. Most importantly, these improvements include a reduction in the levels of fatigue recorded by patients. These findings have not been demonstrated in previous studies of the effect of antidepressant therapy for patients with this illness and this may reflect the short time periods studied in the earlier research.

 

Source: Thomas MA, Smith AP. An investigation of the long-term benefits of antidepressant medication in the recovery of patients with chronic fatigue syndrome. Hum Psychopharmacol. 2006 Dec;21(8):503-9. https://www.ncbi.nlm.nih.gov/pubmed/16981220

 

Chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is thought to have a worldwide prevalence of 0.4-1% with approximately 240,000 patients in the UK. Diagnosis is based on clinical criteria and critically depends on exclusion of other physical and psychiatric diseases. Studies of pathogenesis have revealed immune system abnormalities and chronic immune activation, dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis, brain abnormalities, evidence of emotional stress (comprising host aspects) and evidence of exogenous insults, for example, various microbial infections (Epstein-Barr virus, enteroviruses, parvovirus B19, Coxiella burnetii and Chlamydia pneumoniae), vaccinations and exposure to organophosphate chemicals and other toxins (comprising environmental aspects).

Emotional stress appears to be very important as it reduces the ability of the immune system to clear infections, its presence has been shown to determine whether or not an individual develops symptoms upon virus infection, and it leads to activation of the HPA axis. But, emotional stress is distinct from depression, the presence of which precludes a diagnosis of CFS. There is no specific treatment for CFS other than the much underutilised approach of specific treatment of virus infections. Current priorities are to understand the molecular pathogenesis of disease in terms of human and virus gene expression, to develop a diagnostic test based on protein biomarkers, and to develop specific curative treatments.

 

Source: Devanur LD, Kerr JR. Chronic fatigue syndrome.  J Clin Virol. 2006 Nov;37(3):139-50. Epub 2006 Sep 15. https://www.ncbi.nlm.nih.gov/pubmed/16978917

 

Post-infective and chronic fatigue syndromes precipitated by viral and non-viral pathogens: prospective cohort study

Abstract:

OBJECTIVE: To delineate the risk factors, symptom patterns, and longitudinal course of prolonged illnesses after a variety of acute infections.

DESIGN: Prospective cohort study following patients from the time of acute infection with Epstein-Barr virus (glandular fever), Coxiella burnetii (Q fever), or Ross River virus (epidemic polyarthritis).

SETTING: The region surrounding the township of Dubbo in rural Australia, encompassing a 200 km geographical radius and 104,400 residents.

PARTICIPANTS: 253 patients enrolled and followed at regular intervals over 12 months by self report, structured interview, and clinical assessment.

OUTCOME MEASURES: Detailed medical, psychiatric, and laboratory evaluations at six months to apply diagnostic criteria for chronic fatigue syndrome. Premorbid and intercurrent illness characteristics recorded to define risk factors for chronic fatigue syndrome. Self reported illness phenotypes compared between infective groups.

RESULTS: Prolonged illness characterised by disabling fatigue, musculoskeletal pain, neurocognitive difficulties, and mood disturbance was evident in 29 (12%) of 253 participants at six months, of whom 28 (11%) met the diagnostic criteria for chronic fatigue syndrome. This post-infective fatigue syndrome phenotype was stereotyped and occurred at a similar incidence after each infection. The syndrome was predicted largely by the severity of the acute illness rather than by demographic, psychological, or microbiological factors.

CONCLUSIONS: A relatively uniform post-infective fatigue syndrome persists in a significant minority of patients for six months or more after clinical infection with several different viral and non-viral micro-organisms. Post-infective fatigue syndrome is a valid illness model for investigating one pathophysiological pathway to chronic fatigue syndrome.

 

Source: Hickie I, Davenport T, Wakefield D, Vollmer-Conna U, Cameron B, Vernon SD, Reeves WC, Lloyd A; Dubbo Infection Outcomes Study Group. Post-infective and chronic fatigue syndromes precipitated by viral and non-viral pathogens: prospective cohort study. BMJ. 2006 Sep 16;333(7568):575. Epub 2006 Sep 1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1569956/ (Full article)

 

Current research priorities in chronic fatigue syndrome/myalgic encephalomyelitis: disease mechanisms, a diagnostic test and specific treatments

Abstract:

Chronic fatigue syndrome (CFS) is an illness characterised by disabling fatigue of at least 6 months duration, which is accompanied by various rheumatological, infectious and neuropsychiatric symptoms. A collaborative study group has been formed to deal with the current areas for development in CFS research–namely, to develop an understanding of the molecular pathogenesis of CFS, to develop a diagnostic test and to develop specific and curative treatments. Various groups have studied the gene expression in peripheral blood of patients with CFS, and from those studies that have been confirmed using polymerase chain reaction (PCR), clearly, the most predominant functional theme is that of immunity and defence. However, we do not yet know the precise gene signature and metabolic pathways involved. Currently, this is being dealt with using a microarray representing 47,000 human genes and variants, massive parallel signature sequencing and real-time PCR. It will be important to ensure that once a gene signature has been identified, it is specific to CFS and does not occur in other diseases and infections. A diagnostic test is being developed using surface-enhanced, laser-desorption and ionisation-time-of-flight mass spectrometry based on a pilot study in which putative biomarkers were identified. Finally, clinical trials are being planned; novel treatments that we believe are important to trial in patients with CFS are interferon-beta and one of the anti-tumour necrosis factor-alpha drugs.

 

Source: Kerr JR, Christian P, Hodgetts A, Langford PR, Devanur LD, Petty R, Burke B, Sinclair LI, Richards SC, Montgomery J, McDermott CR, Harrison TJ, Kellam P, Nutt DJ, Holgate ST; Collaborative Clinical Study Group. Current research priorities in chronic fatigue syndrome/myalgic encephalomyelitis: disease mechanisms, a diagnostic test and specific treatments. J Clin Pathol. 2007 Feb;60(2):113-6. Epub 2006 Aug 25. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1860619/ (Full article)

 

Myalgic encephalomyelitis: a review with emphasis on key findings in biomedical research

Abstract:

This review examines research findings in patients with myalgic encephalomyelitis in light of the current debate about this chronic multiple-symptom, multiorgan, multisystem illness and the conflicting views in medicine. These issues cannot be separated from the political opinions and assertions that conflict with science and medicine, and will be part of this review as they have enormous consequences for scientific and medical research, patients, clinicians, carers and policy makers.

 

Source: Hooper M. Myalgic encephalomyelitis: a review with emphasis on key findings in biomedical research. J Clin Pathol. 2007 May;60(5):466-71. Epub 2006 Aug 25. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1994528/ (Full article)

 

Long-chain polyunsaturated fatty acids and the pathophysiology of myalgic encephalomyelitis (chronic fatigue syndrome)

Abstract:

Evidence is put forward to suggest that myalgic encephalomyelitis, also known as chronic fatigue syndrome, may be associated with persistent viral infection. In turn, such infections are likely to impair the ability of the body to biosynthesise n-3 and n-6 long-chain polyunsaturated fatty acids by inhibiting the delta-6 desaturation of the precursor essential fatty acids–namely, alpha-linolenic acid and linoleic acid.

This would, in turn, impair the proper functioning of cell membranes, including cell signalling, and have an adverse effect on the biosynthesis of eicosanoids from the long-chain polyunsaturated fatty acids dihomo-gamma-linolenic acid, arachidonic acid and eicosapentaenoic acid. These actions might offer an explanation for some of the symptoms and signs of myalgic encephalomyelitis.

A potential therapeutic avenue could be offered by bypassing the inhibition of the enzyme delta-6-desaturase by treatment with virgin cold-pressed non-raffinated evening primrose oil, which would supply gamma-linolenic acid and lipophilic pentacyclic triterpenes, and with eicosapentaenoic acid. The gamma-linolenic acid can readily be converted into dihomo-gamma-linolenic acid and thence arachidonic acid, while triterpenes have important free radical scavenging, cyclo-oxygenase and neutrophil elastase inhibitory activities. Furthermore, both arachidonic acid and eicosapentaenoic acid are, at relatively low concentrations, directly virucidal.

 

Source: Puri BK. Long-chain polyunsaturated fatty acids and the pathophysiology of myalgic encephalomyelitis (chronic fatigue syndrome). J Clin Pathol. 2007 Feb;60(2):122-4. Epub 2006 Aug 25. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1860620/ (Full article)

 

A new look at chronic fatigue syndrome/myalgic encephalomyelitis

Abstract:

It has been 3 years since the Chief Medical Officer reported on chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) and the time has come for a thorough investigation by an All Party Group drawn from the House of Commons and the House of Lords. We have received many written submissions and are engaged in taking oral evidence in 2-h sessions, which we open to the public as well as interested groups. The group has received a fantastic response to its requests for written evidence over the past few months.

Questions that arise for a government response are the lack of provision and support for patients with CFS/ME, the issue of the clinical definition of CFS/ME, the need for a diagnostic test for CFS/ME, effectiveness of the National Institute for Clinical Excellence guidelines, and criteria used to decide which treatments are best for patients with CFS or myalgic encephalomyelitis.

 

Source: Gibson I. A new look at chronic fatigue syndrome/myalgic encephalomyelitis.J Clin Pathol. 2007 Feb;60(2):120-1. Epub 2006 Aug 25. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1860614/ (Full article)

 

Special problems of children with myalgic encephalomyelitis/chronic fatigue syndrome and the enteroviral link

Abstract:

Since 1997, it has been known that myalgic encephalomyelitis/chronic fatigue syndrome constitutes the biggest cause of long-term sickness leading to absence from school, in both staff and pupils. The scale of the problem in children is substantial, and the pattern of illness in schools suggests a prominent role for viral infection–for example, the clustering of cases.

The Dowsett-Colby study of 1997, researching long-term sickness, reported on a school roll of 333,024 pupils and 27,327 staff, and found a prevalence of long-term sickness in 70 of 100,000 pupils and 500 of 100,000 staff; 39% of cases were in clusters of three or more. The peak age was 14-16 years. The illness is known to be potentially severe and chronic. In addition, the Tymes Trust has reported that many affected children struggle for recognition of their needs, and are bullied by medical and educational professionals.

Children should have time to recover sufficiently before returning to school; sustainable, energy-efficient and often home-based education is important here to fulfill legal obligations. Research is needed on viruses that trigger childhood myalgic encephalomyelitis–for example, enteroviruses–and on the neurocognitive defects caused by myalgic encephalomyelitis. We should recognise the value of previous biological research and records of outbreaks, and I recommend that myalgic encephalomyelitis be made notifiable owing to the encephalitic nature of the effects commonly reported in this illness.

 

Source: Colby J. Special problems of children with myalgic encephalomyelitis/chronic fatigue syndrome and the enteroviral link. J Clin Pathol. 2007 Feb;60(2):125-8. Epub 2006 Aug 25. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1860612/ (Full article)