Competition for glutathione precursors between the immune system and the skeletal muscle: pathogenesis ofchronic fatigue syndrome

Abstract:

The chronic fatigue syndrome (CFS) is typically associated or follows a recognized or presumed infection. Abnormalities of both humoral and cellular immunity have been demonstrated in a substantial proportion of patients with CFS. The most consistent findings are of impaired lymphocyte responses to mitogen.

As an antioxidant, glutathione (GSH) is essential for allowing the lymphocyte to express its full potential without being hampered by oxiradical accumulation. Hence, protracted challenge of the immunocytes may lead to cellular GSH depletion. Because GSH is also essential to aerobic muscular contraction, an undesirable competition for GSH precursors between the immune and muscular systems may develop.

It is conceivable that the priority of the immune system for the survival of the host has drawn to this vital area the ever-diminishing GSH precursors, thus depriving the skeletal muscle of adequate GSH precursors to sustain a normal aerobic metabolism resulting in fatigue and eventually myalgia.

 

Source: Bounous G, Molson J. Competition for glutathione precursors between the immune system and the skeletal muscle: pathogenesis ofchronic fatigue syndrome. Med Hypotheses. 1999 Oct;53(4):347-9. http://www.ncbi.nlm.nih.gov/pubmed/10608272

 

Melatonin levels in women with fibromyalgia and chronic fatigue syndrome

Abstract:

OBJECTIVE: Fibromyalgia (FM) and chronic fatigue syndrome (CFS) are stress associated disorders mainly affecting women. FM is characterized primarily by widespread musculoskeletal pain, and CFS by profound debilitating fatigue, but there is considerable overlap of clinical symptoms between these 2 syndromes. Neuroendocrine abnormalities have been noted in both FM and CFS and desynchronization of circadian systems has been postulated in their etiology. The pineal hormone melatonin is involved in synchronizing circadian systems and the use of exogenous melatonin has become widespread in patients with FM and CFS.

METHODS: We examined the characteristics and relationship of melatonin and cortisol levels in premenopausal women with FM (n = 9) or CFS (n = 8), compared to age and menstrual cycle phase matched controls. Blood was collected from an indwelling intravenous catheter every 10 min over 24 h, and plasma melatonin and cortisol were determined by radioimmunoassay at 60 and 10 min intervals, respectively.

RESULTS: Night time (23:00-06:50) plasma melatonin levels were significantly higher in FM patients compared to controls (p<0.05), but there was no significant difference in melatonin levels between CFS patients and controls. No differences in the timing of cortisol and melatonin secretory patterns and no internal desynchronization of the 2 rhythms were found in either patient group, compared to controls.

CONCLUSION: Raised plasma melatonin concentrations have been documented in several other conditions that are associated with dysregulation of neuroendocrine axes. Increased melatonin levels may represent a marker of increased susceptibility to stress induced hypothalamic disruptions. These data indicate that there is no rationale for melatonin replacement therapy in patients with FM and CFS.

 

Source: Korszun A, Sackett-Lundeen L, Papadopoulos E, Brucksch C, Masterson L, Engelberg NC, Haus E, Demitrack MA, Crofford L. Melatonin levels in women with fibromyalgia and chronic fatigue syndrome. J Rheumatol. 1999 Dec;26(12):2675-80. http://www.ncbi.nlm.nih.gov/pubmed/10606381

 

Recognition of chronic carbon monoxide poisoning

Abstract:

Chronic exposure to low levels of carbon monoxide can cause vague symptoms that are easily mistaken for other common illnesses. During the past 5 years, three families have contacted the Wisconsin Division of Public Health to report illnesses that may have been caused by chronic exposure to carbon monoxide. Members of these families were diagnosed with a variety of conditions including chronic fatigue syndrome, depression and influenza. Carbon monoxide exposure was not suspected as a cause of these illnesses until heating contractors discovered that gas appliances in these families’ homes were not properly vented. These cases serve as reminders that carbon monoxide exposure should be considered in the differential diagnosis of patients who present with chronic symptoms of headache, fatigue, dizziness, nausea and mental confusion–especially when these symptoms onset during the winter heating season.

 

Source: Knobeloch L, Jackson R. Recognition of chronic carbon monoxide poisoning. WMJ. 1999 Sep-Oct;98(6):26-9. http://www.ncbi.nlm.nih.gov/pubmed/10605352

 

Case of chronic fatigue syndrome after Crimean war and Indian mutiny

Chronic fatigue syndrome was first proposed as a diagnostic label in 1988 to classify a disorder characterised by severe fatigue and exhaustion after minimal physical and mental effort accompanied by other unexplained somatic symptoms.1 It was introduced partly as an acceptable clinical alternative to the term myalgic encephalomyelitis, which described a similar presentation and had been coined in 1956 in the aftermath of an outbreak of illness among the nursing and medical staff of the Royal Free Hospital.2 The condition was widely assumed to be a new addition to the medical scene. In the popular press, and occasionally in the professional publications, attempts have been made to explain chronic fatigue syndrome as a product of the unwelcome features of modern life, such as pollution, stress, working practices, and new infections.

You can read the full article here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1127098/

 

Source: Jones E, Wessely S. Case of chronic fatigue syndrome after Crimean war and Indian mutiny. BMJ. 1999 Dec 18-25;319(7225):1645-7. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1127098/ (Full article)

Psychiatric adjustment in adolescents with a history of chronic fatigue syndrome

Abstract:

OBJECTIVE: To ascertain psychiatric adjustment in youngsters with a history of childhood chronic fatigue syndrome (CFS).

METHOD: Subjects were 25 children and adolescents with CFS who were seen in tertiary pediatric/psychiatric clinics (mean age 15.6 years, seen a mean of 45.5 months after illness onset; 17 subjects had recovered and 8 were still ill) and 15 healthy matched controls. Youngsters and their parents (usually mothers) were interviewed and completed questionnaires. Instruments used included the Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS), the Child Behavior Checklist (CBCL), and the Harter Self-Esteem Questionnaire.

RESULTS: At assessment, psychiatric disorders (mainly anxiety and depressive disorders) were present in half the subjects with a history of CFS, a rate significantly higher than in healthy controls. On the CBCL youngsters with a history of CFS had an excess of psychological symptoms and decreased social competence. On the Harter Self-Esteem Questionnaire they reported reduced self-esteem, especially in social competence. Anxiety disorders were significantly more common in recovered subjects than in those with active CFS illness status.

CONCLUSIONS: Psychiatric disorders were found to be increased in adolescents with a history of severe CFS; CFS may enhance the risk for or share common predisposing factors with anxiety disorders.

Comment in: Chronic fatigue syndrome. [J Am Acad Child Adolesc Psychiatry. 2000]

 

Source: Garralda E, Rangel L, Levin M, Roberts H, Ukoumunne O. Psychiatric adjustment in adolescents with a history of chronic fatigue syndrome. J Am Acad Child Adolesc Psychiatry. 1999 Dec;38(12):1515-21. http://www.ncbi.nlm.nih.gov/pubmed/10596251

 

The 1microg short Synacthen test in chronic fatigue syndrome

Abstract:

OBJECTIVE: Many studies suggest mild hypocortisolism in chronic fatigue syndrome (CFS), usually assumed to be due to reduced suprahypothalamic drive to the hypothalamo-pituitary-adrenal (HPA) axis. We wished to explore further the state of the HPA axis in CFS using the 1 microg low dose short Synacthen test.

DESIGN: Subjects received an intravenous bolus of 1 microg Synacthen; samples for cortisol estimation were taken at baseline and 2, 10, 20, 30, 40 and 60 minutes after injection.

PATIENTS: We tested 20 subjects suffering from CFS according to the criteria of the Center for Diseases Control without psychiatric comorbidity and 20 matched healthy controls. All subjects were drug free for at least 1 month.

MEASUREMENTS: We calculated the cortisol responses to the test as the maximum cortisol attained, the incremental rise in cortisol over baseline (Deltavalue) and as the integrated area under the curve.

RESULTS: There were no significant differences in baseline cortisol or cortisol responses between patients and controls. However, responses generally were low, and many subjects’ peak responses were prior to the standard 30 minute sampling time.

CONCLUSIONS: These results do not lend support to the theory that patients with chronic fatigue syndrome have a low adrenal reserve. However, results from studies assessing the HPA axis are proving to be inconsistent. We suggest that many other factors may be contributing to HPA axis alterations in chronic fatigue syndrome, including sleep disturbance, inactivity, altered circadian rhythmicity, illness chronicity, concomitant medication and comorbid psychiatric disturbance. These sources of heterogeneity need to be considered in future studies, and may explain the inconsistent findings to date.

Comment in: The 1microg Synacthen test in chronic fatigue syndrome. [Clin Endocrinol (Oxf). 2000]

 

Source: Hudson M, Cleare AJ. The 1microg short Synacthen test in chronic fatigue syndrome. Clin Endocrinol (Oxf). 1999 Nov;51(5):625-30. http://www.ncbi.nlm.nih.gov/pubmed/10594524

 

Can we predict recovery in chronic fatigue syndrome?

Abstract:

PURPOSE: To determine if selected demographic or clinical features of chronic fatigue syndrome (CFS) are associated with recovery.

PATIENTS AND METHODS: A follow-up questionnaire was mailed to 341 patients who had been ill on average for nine years to ascertain “recovery” rate (defined as self-reported recovery on a visual analog scale). Baseline demographic and clinical features (functional status and psychological status) recorded at the time of the initial (baseline) clinical visit were analyzed for their association with recovery at the time of follow-up.

RESULTS: Of the 177 patients who responded to the follow-up questionnaire, only 21 (12%) reported “recovery.” Patients with higher levels of physical and social functioning and lower levels of anxiety and obsessive-compulsiveness at baseline were more likely to report recovery at follow-up (p < 0.05). No specific demographic characteristics were associated with recovery.

CONCLUSION: These findings support previous research that complete recovery from CFS is rare and that patients with less severe illness at the initial clinic visit are more likely to have a positive prognosis for recovery. However, considerable overlap in illness severity was observed between the recovered and nonrecovered groups, suggesting that accurate prediction of recovery in individual CFS patients is not currently feasible.

 

Source: Pheley AM, Melby D, Schenck C, Mandel J, Peterson PK. Can we predict recovery in chronic fatigue syndrome? Minn Med. 1999 Nov;82(11):52-6. http://www.ncbi.nlm.nih.gov/pubmed/10589213

 

Chronic fatigue syndrome: new insights and old ignorance

Abstract:

Chronic fatigue syndrome (CFS) is a condition characterized by impairment of neurocognitive functions and quality of sleep and of somatic symptoms such as recurrent sore throat, muscle aches, arthralgias, headache, and postexertional malaise. A majority of patients describe an infectious onset but the link between infections and CFS remains uncertain. Findings show an activation of the immune system, abberations in several hypothalamic-pituitary axes and involvement of other parts of the central nervous system. The origin is bound to be complex and it may well be that the solution will come together with a more generally altered view about mind-body dualism, and the concept of illness and disease.

 

Source: Evengård B, Schacterle RS, Komaroff AL. Chronic fatigue syndrome: new insights and old ignorance. J Intern Med. 1999 Nov;246(5):455-69. http://onlinelibrary.wiley.com/doi/10.1046/j.1365-2796.1999.00513.x/full (Full article)

 

Chronic unexplained fatigue

Abstract:

Fatigue is a common symptom in the community and the commonest associations are with stress or mood disturbance. One in a hundred people complain of unexplained and prolonged fatigue, with half that number meeting the strictest criteria for the chronic fatigue syndrome (CFS). Discrete fatigue syndromes have been described, particularly after Epstein Barr virus infection. The majority of patients with CFS have a syndrome similar to the ICD-10 definition of neurasthenia. Mood and somatoform disorders are common comorbid or differential diagnoses. The prognosis is poor, particularly in patients attending hospitals and those with comorbid psychiatric disorders. The aetiology of both CFS and chronic unexplained fatigue are essentially unknown, perhaps reflecting the heterogenenous natures of both the symptom and syndrome. There is reasonable evidence to suggest that particular infections may trigger both prolonged fatigue and CFS. Maintaining factors are different from triggering factors and include mood and sleep disorders, illness beliefs and behaviours, and possibly inactivity. Treatments aimed at reversing these maintaining factors show promise.

 

Source: White PD. Chronic unexplained fatigue. Acta Neuropsychiatr. 1999 Dec;11(4):130-3. doi: 10.1017/S0924270800035870. http://www.ncbi.nlm.nih.gov/pubmed/26976541

 

Corticomotor excitability and perception of effort during sustained exercise in the chronic fatigue syndrome

Abstract:

OBJECTIVE: We have investigated the possibility of a central basis for the complaints of fatigue and poor exercise tolerance in subjects with chronic fatigue syndrome (CFS).

METHODS: Transcranial magnetic stimulation of the motor cortex was used to measure sequential changes in motor evoked potential (MEP) amplitude, post-excitatory silent period (SP) duration and twitch force of the biceps brachii muscle during a 20% maximum isometric elbow flexor contraction maintained to the point of exhaustion. Ten patients with post-infectious CFS and 10 age- and sex-matched control subjects were studied. Results were analysed using non-parametric repeated measures analysis of variance (Friedman’s test) and Mann-Whitney U-tests for intra- and inter-group comparisons respectively.

RESULTS: Mean endurance time for the CFS group was lower (13.1+/-3.2 min, mean +/- SEM) than controls (18.6+/-2.6 min, P < 0.05) and CFS subjects reported higher ratings of perceived exertion. During the exercise period MEP amplitude and SP duration increased in both groups but to a lesser extent in CFS subjects. Interpolated twitch force amplitude also increased during exercise, being more pronounced in CFS subjects.

CONCLUSION: The findings are in keeping with an exercise-related diminution in central motor drive in association with an increased perception of effort in CFS.

 

Source: Sacco P, Hope PA, Thickbroom GW, Byrnes ML, Mastaglia FL. Corticomotor excitability and perception of effort during sustained exercise in the chronic fatigue syndrome. Clin Neurophysiol. 1999 Nov;110(11):1883-91. http://www.ncbi.nlm.nih.gov/pubmed/10576483