Tag: review

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)

 

Chronic musculoskeletal pain in patients with the chronic fatigue syndrome: a systematic review

Abstract:

BACKGROUND: In addition to debilitating fatigue the majority of patients with chronic fatigue syndrome (CFS) experience chronic widespread pain.

AIMS: Conducting a systematic review to critically assess the existing knowledge on chronic pain in CFS. We focussed on the definition, the prevalence and incidence, the aetiology, the relevance and the therapy strategy for chronic musculoskeletal pain and post-exertional pain in CFS.

METHODS: To identify relevant articles, we searched eight medical search engines. The search terms “chronic fatigue syndrome” AND “pain”, “nociception”, “arthralgia” and “myalgia”, were used to identify articles concerning pain in CFS. Included articles were reviewed by two blinded researchers.

RESULTS: Twenty-five articles and two abstract were identified and selected for further appraisal. Only 11 search results focussed on musculoskeletal pain in CFS patients. Regarding the standardized review of the articles, a 96% agreement between the researchers was observed. There is no consensus in defining chronic widespread pain in CFS, and although there is little or no strong proof for the exact prevalence, chronic pain is strongly disabling in CFS. Aetiological theories are proposed (sleep abnormalities, tryptophan, parovirus-B, hormonal and brain abnormalities and central sensitisation) and a reduction of pain threshold after exercise has been shown. Furthermore depression seemed not related to pain in CFS and a staphylococcus toxoid vaccine caused no significant pain reduction.

CONCLUSIONS: The results from the systematic review highlight the clinical importance of chronic pain in CFS, but only few studies addressing the aetiology or treatment of chronic pain in CFS are currently available.

 

Source: Meeus M, Nijs J, Meirleir KD. Chronic musculoskeletal pain in patients with the chronic fatigue syndrome: a systematic review. Eur J Pain. 2007 May;11(4):377-86. Epub 2006 Jul 13. https://www.ncbi.nlm.nih.gov/pubmed/16843021

 

The debate: myalgic encephalomyelitis and chronic fatigue syndrome

Abstract:

Almost every aspect of myalgic encephalomyelitis (or encephalopathy) and chronic fatigue syndrome is the subject of disagreement and uncertainty — something that has undoubtedly hampered recognition, understanding and research. Although the pathogenesis remains the subject of intense medical debate, a number of predisposing, precipitating and perpetuating factors are now starting to emerge. Therapeutic nihilism is no longer appropriate as there is a great deal that can be done to alleviate some of the more distressing symptoms and improve quality of life for these patients.

 

Source: Shepherd C. The debate: myalgic encephalomyelitis and chronic fatigue syndrome. Br J Nurs. 2006 Jun 22-Jul 12;15(12):662-9. https://www.ncbi.nlm.nih.gov/pubmed/16835542

 

Chronic musculoskeletal pain in chronic fatigue syndrome: recent developments and therapeutic implications

Abstract:

Patients with chronic fatigue syndrome (CFS) experience chronic musculoskeletal pain which is even more debilitating than fatigue. Scientific research data gathered around the world enables clinicians to understand, at least in part, chronic musculoskeletal pain in CFS patients. Generalized joint hypermobility and benign joint hypermobility syndrome appear to be highly prevalent among CFS sufferers, but they do not seem to be of any clinical importance.

On the other hand, pain catastrophizing accounts for a substantial portion of musculoskeletal pain and is a predictor of exercise performance in CFS patients. The evidence concerning pain catastrophizing is supportive of the indirect evidence of a dysfunctional pain processing system in CFS patients with musculoskeletal pain. CFS sufferers respond to incremental exercise with a lengthened and accentuated oxidative stress response, explaining muscle pain, postexertional malaise, and the decrease in pain threshold following graded exercise in CFS patients.

Applying the scientific evidence to the manual physiotherapy profession, pacing self-management techniques and pain neurophysiology education are indicated for the treatment of musculoskeletal pain in CFS patients. Studies examining the effectiveness of these strategies for CFS patients are warranted.

 

Source: Nijs J, Meeus M, De Meirleir K. Chronic musculoskeletal pain in chronic fatigue syndrome: recent developments and therapeutic implications. Man Ther. 2006 Aug;11(3):187-91. Epub 2006 Jun 14. https://www.ncbi.nlm.nih.gov/pubmed/16781183

 

High-resolution magnetic resonance imaging sinc-interpolation-based subvoxel registration and semi-automated quantitative lateral ventricular morphology employing threshold computation and binary image creation in the study of fatty acid interventions in schizophrenia, depression, chronic fatigue syndrome and Huntington’s disease

Abstract:

Serial high-resolution structural magnetic resonance imaging scans of the brain can now be precisely aligned, with six degrees of freedom (three mutually orthogonal translational and three rotational degrees of freedom around three mutually orthogonal axes), using a rigid-body subvoxel registration technique. This is driven by the in-plane point spread function for images acquired in the Fourier domain with data obtained over a bounded region of k-space, namely the sinc interpolation function, where sinc z = (sin z)/z, with z being any complex number (including zero).

Computational subtraction of the three-dimensional Cartesian spatial representation matrices of serially acquired scan data allows for the determination of structural cerebral changes with great precision, since voxel signals from unchanged structures are almost completely cancelled. Thus changes readily show up against a background of noise. Furthermore, lateral ventricular changes can now be accurately quantified using a semi-automated method involving contour production, threshold computation, binary image creation and ventricular extraction.

These techniques have been applied to the investigation of the effects on cerebral structure of intervention with fatty acids, particularly the long-chain polyunsaturated n-3 fatty acid eicosapentaenoic acid (EPA), in disorders such as schizophrenia, treatment-resistant depression, chronic fatigue syndrome (myalgic encephalomyelitis or ME), and Huntington’s disease.

 

Source: Puri BK. High-resolution magnetic resonance imaging sinc-interpolation-based subvoxel registration and semi-automated quantitative lateral ventricular morphology employing threshold computation and binary image creation in the study of fatty acid interventions in schizophrenia, depression, chronic fatigue syndrome and Huntington’s disease. Int Rev Psychiatry. 2006 Apr;18(2):149-54. https://www.ncbi.nlm.nih.gov/pubmed/16777669

Patterns of hypocapnia on tilt in patients with fibromyalgia, chronic fatigue syndrome, nonspecific dizziness, and neurally mediated syncope

Abstract:

OBJECTIVES: To assess whether head-up tilt-induced hyperventilation is seen more often in patients with chronic fatigue syndrome (CFS), fibromyalgia, dizziness, or neurally mediated syncope (NMS) as compared to healthy subjects or those with familial Mediterranean fever (FMF).

PATIENTS AND METHODS: A total of 585 patients were assessed with a 10-minute supine, 30-minute head-up tilt test combined with capnography. Experimental groups included CFS (n = 90), non-CFS fatigue (n = 50), fibromyalgia (n = 70), nonspecific dizziness (n = 75), and NMS (n =160); control groups were FMF (n = 90) and healthy (n = 50). Hypocapnia, the objective measure of hyperventilation, was diagnosed when end-tidal pressure of CO2 (PETCO2) less than 30 mm Hg was recorded consecutively for 10 minutes or longer. When tilting was discontinued because of syncope, one PETCO2 measurement of 25 or less was accepted as hyperventilation.

RESULTS: Hypocapnia was diagnosed on tilt test in 9% to 27% of patients with fibromyalgia, CFS, dizziness, and NMS versus 0% to 2% of control subjects. Three patterns of hypocapnia were recognized: supine hypocapnia (n = 14), sustained hypocapnia on tilt (n = 76), and mixed hypotensive-hypocapnic events (n = 80). Hypocapnia associated with postural tachycardia syndrome (POTS) occurred in 8 of 41 patients.

CONCLUSIONS: Hyperventilation appears to be the major abnormal response to postural challenge in sustained hypocapnia but possibly merely an epiphenomenon in hypotensive-hypocapnic events. Our study does not support an essential role for hypocapnia in NMS or in postural symptoms associated with POTS. Because unrecognized hypocapnia is common in CFS, fibromyalgia, and nonspecific dizziness, capnography should be a part of the evaluation of patients with such conditions.

 

Source: Naschitz JE, Mussafia-Priselac R, Kovalev Y, Zaigraykin N, Slobodin G, Elias N, Rosner I. Patterns of hypocapnia on tilt in patients with fibromyalgia, chronic fatigue syndrome, nonspecific dizziness, and neurally mediated syncope. Am J Med Sci. 2006 Jun;331(6):295-303. https://www.ncbi.nlm.nih.gov/pubmed/16775435