Post-viral fatigue syndrome. Epidemiology: a critical review

Abstract:

Numerous reports in medical journals, lay magazines, and newspapers bear witness to the level of interest in the postviral fatigue syndrome and the heated controversy about the true nature of this condition. For many, it represents a ‘rag bag’ diagnosis into which unsolved diagnostic problems are discarded. Others are in no doubt that there is a discrete syndrome, probably with a specific causation.

The real answer almost certainly lies somewhere in between, but the truth can only be established through epidemiological studies designed to answer key questions. Does it exist at all, and, if so, how frequently does it occur? Who is most likely to get it and what is its cause? What is the nature of its implied association with viral infections and what is the role of other frequently postulated factors, such as psychiatric morbidity? What is its natural history and is there any evidence that any of the treatment/management regimes on offer can effectively lead to symptomatic relief or improve prognosis?

In this chapter, we consider the evidence on these key questions, identify some of the deficiencies in our current knowledge and highlight the kind of research which is still required.

 

Source: Wallace PG. Post-viral fatigue syndrome. Epidemiology: a critical review. Br Med Bull. 1991 Oct;47(4):942-51. http://www.ncbi.nlm.nih.gov/pubmed/1794092

 

History of postviral fatigue syndrome

Abstract:

In writing a history of any illness there is always a dilemma whether to attempt the story of the condition ‘itself’, the medical attempts to define its nature, or to glimpse it via our changing reactions. The easiest is a straightforward account of the attempts of scientists to solve a problem–the classic medical detective story. However, this is often more fiction than fact.

Medicine rarely moves smoothly from ignorance to knowledge, but often in a more circular fashion. A historical approach is thus not solely a record of who did what, but also contributes to our understanding of the problems under scrutiny in this issue. Terminology is never easy in this subject, but the following conventions will be used: The terms neurasthenia and ME will be used in their actual context (as authors themselves used them), without defining either. Post-infectious fatigue syndrome (PIFS) will cover similar conditions when related to infective episodes. All will be used in a neutral fashion, to refer to changing realities as understood by doctors and historians.

This chapter attempts both chronological description and social analysis. The justification for this approach is clear in the case of neurasthenia, since ‘as so little was known of its pathological basis physicians’ statements regarding the disease were composed more of social and cultural elements than of scientific knowledge. Although much has changed, a contemporary account still reveals as much about cultural attitudes as the advance of science.

 

Source: Wessely S. History of postviral fatigue syndrome. Br Med Bull. 1991 Oct;47(4):919-41. http://www.ncbi.nlm.nih.gov/pubmed/1794091

 

Psychiatric perspectives: an overview

Abstract:

This chapter reviews the evidence concerning the importance of psychological and social factors in the aetiology and pathogenesis of chronic fatigue syndrome. The diagnosis is often offered to doctors by patients; and we consider attribution, stigma, collusion between doctor and patient, and abnormal illness behaviour in this context. We then give a brief description of a model for common mental disorders, and show how chronic fatigue syndrome relates to this model. It emerges that there are special vulnerability factors in these patients’ personalities before the viral illness, but the disorder is seen as being released by the viral illness. By the time the disorder becomes established the original causal nexus is seen as no longer so important, and the disorder can be seen as a form of abnormal illness behaviour maintained by special factors. The implications for treatment are then considered.

 

Source: Woods TO, Goldberg DP. Psychiatric perspectives: an overview. r Med Bull. 1991 Oct;47(4):908-18. http://www.ncbi.nlm.nih.gov/pubmed/1794090

 

Treatment of chronic fatigue syndrome

Abstract:

Chronic Fatigue Syndrome is a disorder which is characterised by profound fatigue together with a variety of other subjective clinical features which persist over a prolonged period of time. The aetiology remains at present uncertain and therefore rational therapeutic strategies are difficult to plan. This paper reviews currently used forms of treatment aimed at correcting the possible pathophysiological mechanisms and discusses the problems associated with the management of this condition.

 

Source: McBride SJ, McCluskey DR. Treatment of chronic fatigue syndrome. Br Med Bull. 1991 Oct;47(4):895-907. http://www.ncbi.nlm.nih.gov/pubmed/1794089

 

Muscle biochemistry and pathophysiology in postviral fatigue syndrome

Abstract:

Patients with postviral fatigue syndrome (PVFS) usually complain of the skeletal muscle-related symptoms of fatigue and myalgia. It is not surprising therefore that the muscles have recently been the object of intensive studies which have used a variety of biochemical and physiological techniques. The aim of this chapter is to review these findings, and to discuss their significance or otherwise to the presenting symptoms and course of the condition.

 

Source: Edwards RH, Newham DJ, Peters TJ. Muscle biochemistry and pathophysiology in postviral fatigue syndrome. Br Med Bull. 1991 Oct;47(4):826-37. http://www.ncbi.nlm.nih.gov/pubmed/1794087

 

Neurophysiology of postviral fatigue syndrome

Abstract:

The exact pathophysiology of excessive fatigue in patients with postviral fatigue syndrome (PVFS) remains uncertain in spite of increasing investigation. One objective abnormality of neuromuscular function is the increased jitter on single fibre EMG studies. While this is a sensitive technique which indicates a disturbance in the peripheral part of the motor unit, it is non-specific and its role in the pathophysiology remains unclear.

Impaired muscular activation with added force in response to superimposed electrical stimulation suggests an extra-muscular and/or central component of fatigue. Conventional neurophysiological studies and those of strength and endurance have shown no objective abnormality in patients compared with controls. The previous reports of disturbed muscle metabolism on NMR spectroscopy have not been confirmed in more recent studies and no consistent abnormality of excitation-contraction coupling has so far emerged.

Finally, unlike patients with depression, cognitive evoked potential studies suggest impaired attention, memory and stimulus evaluation in postviral fatigue syndrome. In future studies, the importance of utilising approved clinical criteria for patient inclusion cannot be overemphasized. Control groups should include sedentary or deconditioned as well as depressed subjects to help standardise these important variables.

 

Source: Jamal GA, Miller RG. Neurophysiology of postviral fatigue syndrome. Br Med Bull. 1991 Oct;47(4):815-25. http://www.ncbi.nlm.nih.gov/pubmed/1794086

 

Clinical spectrum of postviral fatigue syndrome

Abstract:

Many different neurological and psychiatric syndromes follow viral infections, but their clinical pictures and pathogeneses are poorly understood. The syndromes include acute disseminated encephalomyelitis (post-infectious encephalomyelitis), the Guillain-Barre syndrome (post-infectious neuritis) and Reye’s syndrome.

Recently, attention has been focused on another common postviral neurological syndrome, i.e. the postviral fatigue syndrome (PVFS)–termed myalgic encephalomyelitis (ME) and a host of other designations. PVFS occurs both sporadically and in epidemics, with cases being reported from all over Europe, the United States, Australasia and South Africa.

It is difficult to make the diagnosis and this has meant, in the past, that it is not until an epidemic has occurred that random cases which presented in the preceding years are realised to represent the same condition. With renewed interest in the syndrome and greater attention from physicians, however, diagnosis of sporadic cases is now becoming more common.

 

Source: Behan PO, Bakheit AM. Clinical spectrum of postviral fatigue syndrome. Br Med Bull. 1991 Oct;47(4):793-808. http://www.ncbi.nlm.nih.gov/pubmed/1794085

 

Myalgic encephalomyelitis

Comment on: Myalgic encephalomyelitis. [J R Soc Med. 1991]

 

The exchange of views between Drs Wessely and Wilson in the correspondence columns of the March issue of the Journal (March 1991 JRSM, p 182) highlights the divergence of opinion concerning the nature of myalgic encephalomyelitis (ME).

Recognition of ME as a significant health problem in New Zealand dates from an outbreak of ‘Tapanui ‘flu’ in a small country town in 1983. As it seemed possible that the wide range of symptoms could be indicative of impaired capillary blood flow, we studied the filtrability of blood samples from members of ME support groups. We found that subjects who were acutely unwell had prolonged blood filtration times which returned towards normal in the chronic state.

More recently it has been shown that ME symptoms are associated with increased percentages of nondiscocytic erythrocytes and the percentage of such cells showed an inverse correlation with wellbeing. The significance of altered red cell shape in the pathogenesis of ME has been discussed and it has been found that an injection of vitamin B12 improved wellbeing within 24 h. The loss of symptoms was associated with reduced percentages of nondiscocytes in about 50% of subjects. Those who failed to perceive a beneficial response from the B12 showed no change in red cell shape. Further studies at varying degrees of completion confirm and extend the published observations.

You can read the rest of this comment here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1295578/pdf/jrsocmed00119-0075a.pdf

 

Source: Simpson LO. Myalgic encephalomyelitis. J R Soc Med. 1991 Oct;84(10):633. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1295578/

 

Immunology of postviral fatigue syndrome

Abstract:

Postviral fatigue syndrome is associated with persistent infection by a virus. The patient with the condition has failed to eliminate the virus in the usual time. There is little evidence of a deficient immune response by the patient as the explanation for the viral persistence, and it must be assumed that most of the explanation lies in down-regulation of virus expression in infected cells. The general symptomatology of postinfectious syndromes may be mediated by cytokines liberated as part of the infection. Part of the syndrome may also be due to local effects of virus infection in muscles or the central nervous system (CNS).

 

Source: Mowbray JF, Yousef GE. Immunology of postviral fatigue syndrome. Br Med Bull. 1991 Oct;47(4):886-94. http://www.ncbi.nlm.nih.gov/pubmed/1724405

 

Amplification and identification of enteroviral sequences in the postviral fatigue syndrome

Abstract:

Evidence from several sources has long suggested that enteroviruses might play a role in the postviral fatigue syndrome (PVFS).

We used the most sensitive molecular virological method available at present, the polymerase chain reaction (PCR) amplification technique, to look for enteroviral copies in peripheral blood leucocytes and muscle from a well-defined group of patients. We demonstrated that our PCR method amplified a sequence common to a wide range of enteroviral serotypes. A highly significant number of the muscle biopsies (53%: P = less than 0.001) from the patients were positive for enteroviral sequences. With regard to the leucocyte samples, 16% in both patient and control were positive.

The PCR results on the peripheral blood leucocytes were in keeping with serological findings, in showing that the level of exposure to enteroviruses seemed to be the same in patients and controls: it was therefore of the greatest interest that patients were 6.7 times more likely to have enteroviral genome in their muscle.

We conclude that persistent enteroviral infection plays a role in the pathogenesis of PVFS, also providing preliminary evidence that severe mitochondrial injury is one of the mechanisms involved.

 

Source: Gow JW, Behan WM. Amplification and identification of enteroviral sequences in the postviral fatigue syndrome. Br Med Bull. 1991 Oct;47(4):872-85. http://www.ncbi.nlm.nih.gov/pubmed/1665380