The chronic fatigue syndrome: a return to common sense

The chronic fatigue syndrome has become one of the past decade’s causes celebres, vying with ecological issues for a place in the public perception of real and imagined threats to society and the individual. Perhaps this interest is a manifestation of the malaise of fin de siecle which in other ages has led to outbursts of anarchy’ or increased eschatological preoccupation. Fortunately, the passing of time-and the cathartic benefits of publication have restored a more reasoned view of chronic fatigue and its attendant problems. Chronic fatigue first became prominent as one of the features of myalgic encephalomyelitis or the ‘ME syndrome’ and has subsequently been the subject of intense debate. (2’5) In truth, fatigue is a symptom with many causes and is thus comparable with dyspnoea or dyspepsia. However, in some patients it is the dominant complaint, thereby defining chronic fatigue as a syndrome sui generis in the minds of some observers.

You can read the rest of this article here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2429649/pdf/postmedj00163-0004.pdf

 

Source: Denman AM. The chronic fatigue syndrome: a return to common sense. Postgrad Med J. 1990 Jul;66(777):499-501. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2429649/

 

Post-viral fatigue syndrome, viral infections in atopic eczema, and essential fatty acids

Abstract:

Three clinical observations relating to viral infections are well-known but poorly understood. These are: the susceptibility of people with atopic eczema to viral infections; the occasional precipitation of an atopic syndrome by viral infections; the occurrence of a fatigue syndrome following viral infections.

A unifying hypothesis is presented which explains these observations in terms of the interactions between viral infections and essential fatty acid (EFA) metabolism. Key elements of the hypothesis are the facts that interferon requires 6-desaturated EFAs in order to exert its anti-viral effects, that people with atopic eczema have low levels of 6-desaturated EFAs, and that viruses, as part of their attack strategy, may reduce the ability of cells to make 6-desaturated EFAs.

The hypothesis has practical implications for the treatment of patients with viral infections.

 

Source: Horrobin DF. Post-viral fatigue syndrome, viral infections in atopic eczema, and essential fatty acids.  Med Hypotheses. 1990 Jul;32(3):211-7.  http://www.ncbi.nlm.nih.gov/pubmed/2204789

 

Chronic fatigue syndrome–a new disease picture?

Abstract:

The chronic fatigue syndrome has recently been more frequently diagnosed. Yet it is unknown if this syndrome represents a disease entity of its own or merely a diagnostic label for a miscellaneous group of disorders. Further investigations are needed to find out if the syndrome has an organic or psychosomatic aetiology, or a mixture of both. In the meantime it is the responsibility of the clinician to make this decision in each individual case.

 

Source:  Nix WA. Chronic fatigue syndrome–a new disease picture? Nervenarzt. 1990 Jul;61(7):390-6. [Article in German] http://www.ncbi.nlm.nih.gov/pubmed/2202912

 

Myalgic encephalomyelitis–a persistent enteroviral infection?

Abstract:

Myalgic encephalomyelitis is a common disability but frequently misinterpreted. Amongst 6,000 patients referred for general microbiological diagnosis between 1975 and 1987, 420 cases were recognized.

Coxsackie B neutralization tests, in 205 of these, demonstrated significant titres in 103/205 (50%), while of 124 additionally investigated for enteroviral IgM, 38/124 (31%) were positive. This illness is distinguished from a variety of other post-viral states by an unique clinical and epidemiological pattern characteristic of enteroviral infection.

Prompt recognition and advice to avoid over-exertion is mandatory. Routine diagnosis, specific therapy and prevention, await further technical advances.

 

Source:  Dowsett EG, Ramsay AM, McCartney RA, Bell EJ. Myalgic encephalomyelitis–a persistent enteroviral infection? Postgrad Med J. 1990 Jul;66(777):526-30. http://www.ncbi.nlm.nih.gov/pubmed/2170962

Note: You can read the full article here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2429637/

 

The diagnosis of postviral syndrome

Note: This comment appeared in Journal of the Royal Society of Medicine Volume 83 June 1990. You can view the table referenced in the comment here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1292703/pdf/jrsocmed00135-0083a.pdf

 

The difficulty of making a definitive diagnosis of postviral syndrome (myalgic encephalomyelitis) is emphasized by Dr Bowman and his colleagues (December 1988 JRSM, p 712).

After a patient with this condition reported benefit from hyperbaric oxygen (HBO) (1), 36 other patients requested to be treated at Centres administered by ‘Action and Research for Multiple Sclerosis’ (ARMS). Thirty had been investigated in hospital.

They received 20 daily one hour sessions breathing 100% oxygen under pressure. Thirteen patients reported symptomatic improvement at 1.25 atmospheres absolute (ata), 10 responded at 1.5 ata, three at 1.75 ata and two at 2.0 ata.

The patients were asked to record any changes in their symptoms at the end of the course and their accumulated replies are given in Table 1.

A speculative explanation is that high concentrations of oxygen may limit the excessive intracellular lactic acid in skeletal muscle that has been demonstrated in this disease(2). The clinical pattern of myalgic encephalomyelitis has much in common with multiple sclerosis and it is possible that some of these patients had, in fact, got MS.

However, muscle pains are seldom a feature of MS, while they occurred in all but four of these patients. Seventeen out of the 33 with this symptom reported improvement, a response to HBO which might be elaborated into a therapeutic test.

ARMS treated these patients (with the consent of their doctors) on an empirical basis, and it is not implied that HBO is a definitive treatment for ME. However, these reports of subjective improvement suggest that a formal trial should be initiated.

~D J D PERRINS Adviser on Hyperbaric Medicine to ARMS, 4a Chapel Hill, Stansted, Essex CM24 8AG

 References

1 Newsletter of the M.E. Association No 21, 1986

2 Arnold DL, Bore PJ, Radda GK, et al. Excessive intracellular acidosis of skeletal muscle on exercise in a patient with a post-viral exhaustion/fatigue syndrome. Lancet 1984;i:1367-9

 

Source: D J Perrins. The diagnosis of postviral syndrome.  J R Soc Med. 1990 Jun; 83(6): 413. PMCID: PMC1292703  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1292703/

 

Immunologic abnormalities in chronic fatigue syndrome

Abstract:

The chronic fatigue syndrome (CFS), formerly known as chronic Epstein-Barr virus syndrome, is a clinical state of some complexity and uncertain etiology. In order to characterize in a comprehensive manner the status of laboratory markers associated with cellular immune function in patients with this syndrome, 30 patients with clinically defined CFS were studied.

All of the subjects were found to have multiple abnormalities in these markers. The most consistent immunological abnormality detected among these patients, when compared with normal controls, was low natural killer (NK) cell cytotoxicity. The number of NK cells, as defined by reactivity with monoclonal antibody NKH.1 (CD56), was elevated, but the killing of K562 tumor cells per CD56 cell was significantly diminished.

Lymphoproliferative responses after stimulation with phytohemagglutinin and pokeweed mitogen were decreased in most patients when compared with those in normal controls, as was the production of gamma interferon following mitogen stimulation. Lymphocyte phenotypic marker analysis of peripheral blood lymphocytes showed that there were significant differences between patients with CFS and controls.

There was an increase in the percentage of suppressor-cytotoxic T lymphocytes, CD8, and a proportionally larger increase in the number of CD8 cells expressing the class II activation marker. Most patients had an elevated number of CD2 cells which expressed the activation marker CDw26. The numbers of CD4 cells and the helper subset of CD4+CD29+ cells in patients with CFS were not different from those in controls. There was, however, a significant decrease in the suppressor inducer subset of CD4+ CD45RA+ cells. The number of B cells, CD20 and CD21, were elevated, as were the numbers of a subset of B cells which coexpressed CD20 and CD5.

The patterns of immune marker abnormalities observed was compatible with a chronic viral reactivation syndrome.

 

Source: Klimas NG, Salvato FR, Morgan R, Fletcher MA. Immunologic abnormalities in chronic fatigue syndrome. J Clin Microbiol. 1990 Jun;28(6):1403-10. http://www.ncbi.nlm.nih.gov/pubmed/2166084

Note: You can read the full article here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC267940/

 

Persistence of enteroviral RNA in chronic fatigue syndrome is associated with the abnormal production of equal amounts of positive and negative strands of enteroviral RNA

Abstract:

A subgenomic restriction fragment from cDNA prepared from Coxsackie B2 virus (CVB2) RNA was subcloned into a riboprobe vector allowing the production of enteroviral group-specific RNA probes complementary to either the positive (genomic) or negative (template) strand of enteroviral RNA. These riboprobes were used to follow productive infection of cultured cells by CVB2; as expected, positive strand RNA was synthesized in approximately 100-fold excess over negative strand.

RNA was extracted from muscle biopsy samples from patients with chronic fatigue syndrome and probed for the presence of enteroviral RNA. In cases where enteroviral RNA was detected the amounts of positive and negative strands of enteroviral RNA were approximately equal, in contrast to the situation in lytic infection of cultured cells.

This suggests that enterovirus persistence in muscle is due to a defect in control of viral RNA synthesis.

 

Source: Cunningham L, Bowles NE, Lane RJ, Dubowitz V, Archard LC. Persistence of enteroviral RNA in chronic fatigue syndrome is associated with the abnormal production of equal amounts of positive and negative strands of enteroviral RNA. J Gen Virol. 1990 Jun;71 ( Pt 6):1399-402. http://www.ncbi.nlm.nih.gov/pubmed/2161907

 

Depression and myalgic encephalomyelitis

This comment, published in the Journal of the Royal Society of Medicine in May 1990, was written in response to a letter by Dr. Lev. You can read the letter here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1292388/

 

We read the letter from Lev (November 1989 JRSM, p 693) with interest, but see a danger in using assumptions as to aetiology in definition of study groups. Operational definitions not making this assumption will produce replicable findings and progress towards better definitions and understanding of aetiology.

Definitions of depressed control groups are difficult, for example the following need to be controlled:

(1) Demographic variables

(2) Severity of depression symptoms: inappropriate control groups for ME patients would be severely depressed inpatients. Outpatient depressives are not too dissimilar in severity.

(3) Psychotropic medication: this is less likely to be given to ME patients where treatment is not agreed and could modify symptoms to be compared.

(4) Psychiatric history: in possible ME patients a previous significant psychiatric illness prior to fatigue symptoms leads to difficulty in studying this symptom and produces too much overlap with depressed controls.

(5) History of febrile illness: to minimize overlap, one must also control for preceding febrile illness in otherwise typical depressive illness.

Comparison of control groups should be serial, not cross-sectional as physical symptoms and markers may fluctuate, as may fatigue and depression.

Assessment of depressive symptoms is difficult, as Lev points out, due to non-specific ‘biological’ symptoms of depression. However, psychic ones such as pessimism should not overlap and could be assessed.

The concept of fatigue is poorly understood, as is its assessment. The paradigm of pain research has much to offer, where ‘dichotomization’ of physical and psychological components is not thought useful, but assessment emphasizes all components of the experience of pain. Thus, psychometric assessment of fatigue, for example, its severity, frequency, and pattern may be a future research area. Using such a paradigm, our initial findings of differences in fatigue in the two groups are because depressed patients are predominantly anergic, but ‘ME’ patients have more variability and unpredictable onset of fatigue relative to the severity of exercise attempted. Lack of motivation overlaps in both groups, explicable in Lev’s own terms as due to a reaction to a chronic illness.

~SEAN LYNCH Lecturer and Honorary Senior Registrar in Psychiatry

~RAM SETH Senior Registrar in Psychiatry St Charles Hospital, London

 

Source: S Lynch and R Seth. Depression and myalgic encephalomyelitis. J R Soc Med. 1990 May; 83(5): 341. PMCID: PMC1292666. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1292666/pdf/jrsocmed00136-0073a.pdf

 

The low yield of physical examinations and laboratory investigations of patients with chronic fatigue

Abstract:

Fatigue is a common symptom but guidelines for its appropriate evaluation are lacking. The authors prospectively studied 100 adults with a chief complaint of fatigue lasting at least 1 month in order to determine the diagnostic contribution of physical examinations and laboratory investigations.

The evaluations were performed in the specialized clinic of a faculty practice. Physical examinations produced diagnostic information in 2% of patients, and laboratory investigations elucidated the cause of fatigue in 5% of patients. Structured follow-up evaluations after an average interval of 10 months failed to reveal any new organic causes for the fatigue symptom. Minor laboratory abnormalities were relatively common but did not contribute to the diagnostic process and did not seem to influence the clinical outcome.

The authors conclude that the traditional medical evaluation of patients complaining of chronic fatigue has a low yield in discovering treatable physical disorders.

 

Source:  Lane TJ, Matthews DA, Manu P. The low yield of physical examinations and laboratory investigations of patients with chronic fatigue. Am J Med Sci. 1990 May;299(5):313-8. http://www.ncbi.nlm.nih.gov/pubmed/2337122

 

The psychiatric status of patients with the chronic fatigue syndrome

Abstract:

The prevalence of psychiatric disorder in 48 patients with chronic fatigue syndrome (CFS) was determined. Twenty-two had had a major depressive (non-endogenous) episode during the course of their illness, while seven had a current major (non-endogenous) depression.

The pre-morbid prevalence of major depression (12.5%) and of total psychiatric disorder (24.5%) was no higher than general community estimates. The pattern of psychiatric symptoms in the CFS patients was significantly different to that of 48 patients with non-endogenous depression, but was comparable with that observed in other medical disorders. Patients with CFS were not excessively hypochondriacal.

We conclude that psychological disturbance is likely to be a consequence of, rather than an antecedent risk factor to the syndrome.

 

Source: Hickie I, Lloyd A, Wakefield D, Parker G. The psychiatric status of patients with the chronic fatigue syndrome. Br J Psychiatry. 1990 Apr;156:534-40. http://www.ncbi.nlm.nih.gov/pubmed/2386862