Chronic fatigue syndrome update. Findings now point to CNS involvement

Abstract:

Neither Epstein-Barr virus nor human herpesvirus 6 appears to play a causative role in chronic fatigue syndrome. The possibility that a novel human retrovirus may be present in patients with the syndrome needs further study. A number of abnormalities found in patients with chronic fatigue syndrome point to central nervous system (CNS) involvement. These include immunologic abnormalities, indications of pituitary and hypothalamic involvement, abnormal basal plasma levels of certain neurotransmitter metabolites, and cerebral perfusion abnormalities. The symptom pattern of chronic fatigue syndrome may eventually be explainable in terms of CNS dysfunction.

 

Source: Bell DS. Chronic fatigue syndrome update. Findings now point to CNS involvement. Postgrad Med. 1994 Nov 1;96(6):73-6, 79-81. http://www.ncbi.nlm.nih.gov/pubmed/7971614

 

Enteroviruses and the chronic fatigue syndrome

Abstract:

The possible role of enteroviral persistence in the etiology of the chronic fatigue syndrome (CFS) was investigated by serological testing, VP-1 antigen testing, and polymerase chain reaction (PCR) analysis of stool specimens as well as by viral cultures of stool–both direct and after acid treatment. No differences between 76 patients with disabling unexplained fatigue and 76 matched controls were found by serological or antigen testing.

Furthermore, no enteroviruses were isolated from any stool culture. Enterovirus was detected by PCR in one stool specimen from a patient with CFS but was not detectable in a second sample obtained from the same patient 3 months later. All stool specimens from controls were PCR-negative. These results argue against the hypothesis that enteroviruses persist in patients with CFS and that their persistence plays a role in the pathogenesis of this syndrome.

 

Source: Swanink CM, Melchers WJ, van der Meer JW, Vercoulen JH, Bleijenberg G, Fennis JF, Galama JM. Enteroviruses and the chronic fatigue syndrome. Clin Infect Dis. 1994 Nov;19(5):860-4. http://www.ncbi.nlm.nih.gov/pubmed/7893870

 

Psychobehavioral and immunological characteristics of adult people with chronic fatigue and patients with chronic fatigue syndrome

Abstract:

The psychobehavioral responses and cellular immune function were investigated in healthy people (control, N = 21), adult people with chronic fatigue (fatigue-non-CFS group, N = 24), and patients with chronic fatigue syndrome (CFS, N = 10).

Based on psychobehavioral responses, the fatigue-non-CFS group had low general activity levels (p < .05) and slightly depressive tendencies (p < .01) compared with the control. They had many life event stresses (p < .05) and sleep disturbances (p < .01), and they could not cope appropriately with stresses.

The fatigue-non-CFS group also showed significantly lower natural killer (NK) cell activity (p < .01) and decreased numbers of CD16+ and CD56+ cells (p < .05). Compared with the fatigue-non-CFS group, patients with CFS had higher degrees of physical fatigue (p < .01) and more life event stresses (p < .05).

They had lower general activity levels and social introversion. They were also in a depressive state. NK cell activity and the numbers of CD16+ and CD56+ cells were significantly reduced in patients with CFS (p < .01).

These findings suggest that adult people with chronic fatigue may be in an intermediate state between the healthy control and patients with CFS in terms of psychobehavioral responses and low NK cell activity. We observed three cases in such an intermediate state in whom CFS subsequently developed.

 

Source: Masuda A, Nozoe SI, Matsuyama T, Tanaka H. Psychobehavioral and immunological characteristics of adult people with chronic fatigue and patients with chronic fatigue syndrome. Psychosom Med. 1994 Nov-Dec;56(6):512-8. http://www.ncbi.nlm.nih.gov/pubmed/7871106

 

Research about fatigue in France over the past 20 years

Abstract:

The author reported the works of the “Fatigue Studies Group” founded 20 years ago to explore the different dimensions of “fatigue” complaint. The emphasis is placed on the asthenic syndromes evaluation instrument created by the group, which takes into account the socio-demographic data of the patient, clinical signs and their severity as well as the potential etiological factors. Its first version (GEF-3) enabled to isolate 4 groups of asthenia (overworking, somatic, psychosomatic and psychic), each of them requesting a specific treatment. An ulterior version (GEF-4) has been elaborated to describe better the psychiatric semeiology. Finally, a simplified version (GEF-10) was used as an evaluation instrument in different therapeutic researches. At the same time, the group continued its researches on the fatigue psychosocial dimensions and its nosographic status, especially in comparison with dysthymic disorders.

 

Source: Crocq L. Research about fatigue in France over the past 20 years. Encephale. 1994 Nov;20 Spec No 3:615-8. [Article in French] http://www.ncbi.nlm.nih.gov/pubmed/7843059

 

Current studies on the neurobiology of chronic fatigue syndrome

Abstract:

Cytokines are soluble mediators which are released by activated immune cells during infection and inflammation. The possibility that fatigue is mediated by the effects of cytokines on the central nervous system is supported by several converging lines of evidence: 1) infusions of cytokines to immunocompromised patients induce flu-like symptoms including fatigue and malaise; 2) peripheral and central injection of cytokines to laboratory rodents induce sickness behaviour; 3) symptoms of sickness behaviour occurring during experimental infections can be abrogated by administration of anti-cytokine treatments; 4) although many pitfalls in the detection of cytokines still exist, patients afflicted with the chronic fatigue syndrome have been found in some studies to display instances of excessive production of cytokines.

Experimental studies have confirmed that cytokines are interpreted by the brain as internal signals for sickness. Furthermore, there is evidence that sickness is a motivation which reorganizes the organism’s priorities in face of this particular threat which is represented by infectious pathogens. The elucidation of the mechanisms that are involved in these effects and in particular, the role of the cytokines which are produced in the brain in response to peripheral immune stimuli and to stressors, should give new insight on the way sickness and recovery processes are organized in the brain.

 

Source: Dantzer R. Current studies on the neurobiology of chronic fatigue syndrome. Encephale. 1994 Nov;20 Spec No 3:597-602. [Article in French] http://www.ncbi.nlm.nih.gov/pubmed/7843056

Chronic fatigue syndrome. Clinical, social psychological problems and management

Abstract:

Fatigue chronic syndrome (SFC) is the heir-at-law of neurasthenia. Both are seen like physical diseases and share certain therapeutic measures, such as sleep; they have the same symbolic function and enable patients as well as doctors reluctant to psychological dimensions of pathology, to get and express sympathy and attention. A strong controversy developed these last years concerning the SFC physiopathology particularly concerning the responsibility of viral infectious agents or psychiatric troubles.

The SFC fatigue is unlikely hysterical or neuromuscular but it probably depends on several associated factors; cerebral neurobiochemistry anomalies (possibly induced by an infection or immune reactions), effort perception trouble, affective trouble, lack of physical activity. The handicap seems to be worse on account of unsuitable care and inefficacious treatment. Especially sleep, which is often beneficial in a short term, is source of ulterior chronicisation. Antidepressants are the only justified pharmacological treatment for SFC at the moment. Referring to the existence and the nature of cognitive distortions, the author suggests a cognitive-behavioural therapy, whose aim is a progressive activity resumption.

 

Source: Wessely S. Chronic fatigue syndrome. Clinical, social psychological problems and management. Encephale. 1994 Nov;20 Spec No 3:581-95. [Article in French] http://www.ncbi.nlm.nih.gov/pubmed/7843055

 

Epidemiologic study of chronic fatigue in primary care (general practice)

Abstract:

The results of a cross sectional study of fatigue in two large samples of patients attending primary care physicians are reported. The level of complaint of fatigue was higher in the prospective sample, which consisted of patients who had been diagnosed as suffering from a viral infection six months earlier. Duration and frequency of experience of fatigue correlated with severity in both samples. Severity, duration and frequency were continuously distributed in these populations.

Attribution of fatigue in these two samples was mixed: social stresses, current physical illness and psychological problems all being offered as explanations. 11% of the cross sectional sample and 17% of the prospective sample met study operational criteria for a possible chronic fatigue state. These patients were assessed in greater detail. The majority had a diagnosable psychiatric disorder, predominantly depression. Physical illnesses were not adequate to explain these fatigue states.

These studies in primary care do not support a clinical entity of a “chronic fatigue syndrome”. Some patients in primary care settings have complaints of fatigue that are both disabling and long lasting, but they do not form a distinct group although the majority are likely however to be suffering from a concurrent psychiatric disorder. In contrast to similar patients with chronic fatigue syndromes attending hospital clinics, primary care patients with complaints of fatigue are much more varied in their ideas of causation with considerable less evidence of disease conviction.

 

Source: Mann AH, Mc Donald E, Cope H, Pelosi A, David A. Epidemiologic study of chronic fatigue in primary care (general practice). Encephale. 1994 Nov;20 Spec No 3:575-9. [Article in French] http://www.ncbi.nlm.nih.gov/pubmed/7843054

 

Neurasthenia, yesterday and today

Abstract:

Neurasthenia was described and explained in very mechanistic terms, at the end of the 19th century, by G.M. Beard to account for physical and mental exhaustion and for varied somatic troubles imputed to failure of too much solicited nervous resources. This concept was then universally adopted and gave rise to diverse interpretations, among which was the Freud’s one. Later, in Occident, came a deterioration, the diagnostic of neurasthenia giving way to those of anxious or affective disorders. In the same time, at least for ideological and cultural reasons, the concept remained lively in Russia and in Asia. During the last decade the western psychiatry has been led to accept that there are clinical situations focussed on fatigue and fatigability, even if it coined for them new terminologies (post-infectious fatigue, chronic fatigue syndrome, etc.) and while DSMs keep on ignoring neurasthenia, the ICD 10 gives it an important place.

 

Source: Pichot P. Neurasthenia, yesterday and today. Encephale. 1994 Nov;20 Spec No 3:545-9.[Article in French] http://www.ncbi.nlm.nih.gov/pubmed/7843049

 

Influence of patients’ expectations on disease

EDITOR,-Michael Loudon continues the debate about the contribution of psychological factors to the development of the chronic fatigue syndrome and the influence of patients’ expectations on the prognosis.

I developed glandular fever over a year ago. For three months earlier this year I had considerable but variable difficulty in getting out of bed in the morning, muscle “woodenness” all over, and wobbly legs in association with a still positive PaulBunnell test. Normal activities have not been a problem for some time now, but I am still struggling to resume sporting activities at something like my previous level.

Why do we seek to make general statements? It is so easy to illustrate the futility of trying to generalise. For example, the teenage son of one of my colleagues on the nursing staff at our hospice died of hepatitis arising from the early stages of glandular fever, despite his transfer to a liver unit. By contrast, I had a normal appetite from the beginning of my illness and no abdominal tenderness. If this lad died of hepatitis and I had no hepatitis at all, does anyone suggest that he did not have a helpful attitude to his illness, while I did to mine? I think not. Why not? Because when we understand and can measure we accept that there is a range of organically based illness.

Surely the reason why there is scepticism about whether the chronic fatigue syndrome has an organic basis is because of the implications for long term absenteeism from work as well as the cost to the country in benefits.

You can read the rest of this comment here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2541947/pdf/bmj00463-0066e.pdf

 

Source: Ife S. Influence of patients’ expectations on disease. BMJ. 1994 Oct 29;309(6962):1160-1. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2541947/

 

MELISA-an in vitro tool for the study of metal allergy

Abstract:

The sensitizing properties of metals widely used in medical and dental care have been studied with the help of an optimized lymphocyte proliferative assay, MELISA. MELISA (memory lymphocyte immuno-stimulation assay) was originally developed for the screening of allergenic epitopes of drugs and other chemicals of low molecular weight, but has recently been adapted for the study of metal-induced sensitization.

The patients studied suffered from various oral mucosal problems which were suspected to be caused by the release of metal ions from dental restorations. They were also troubled by chronic fatigue persisting over many years. One patient was also occupationally exposed to metals while working in a dental practice. Healthy subjects without any discomfort due to metal devices served as controls. In addition to metals used in dentistry, lymphocyte responses to organic mercurials used widely as preservatives in vaccines, eye/nose drops and contact lense fluids were studied.

The results indicated that mercurials, as well as other metals such as gold or palladium, induce strong lymphocyte proliferative responses in patients with oral or systemic symptoms, but not in similarly exposed unaffected subjects.

The results of MELISA performed with a pair of identical twins with chronic fatigue syndrome (CFS) indicated that metal-specific responses may be dependent on the genetics of the patient. Thus, many metals that are today accepted for use in medicine and dentistry carry a definite sensitizing risk for certain genetically predisposed individuals. Therefore, the use of these metals should be limited in the future.

 

Source: Stejskal VD, Cederbrant K, Lindvall A, Forsbeck M. MELISA-an in vitro tool for the study of metal allergy. Toxicol In Vitro. 1994 Oct;8(5):991-1000. http://www.ncbi.nlm.nih.gov/pubmed/20693060