Chronic fatigue syndrome

Abstract:

During the past two decades, there has been heated debate about chronic fatigue syndrome (CFS) among researchers, practitioners, and patients. Few illnesses have been discussed so extensively. The existence of the disorder has been questioned, its underlying pathophysiology debated, and an effective treatment opposed; patients’ organisations have participated in scientific discussions.

In this review, we look back on several controversies over CFS with respect to its definition, diagnosis, pathophysiology, and treatment. We review issues of epidemiology and clinical manifestations, focusing on the scientific status of CFS. Modern neuroscience and genetics research offer interesting findings for new hypotheses on the aetiology and pathogenesis of the illness. We also discuss promising future issues, such as psychopathophysiology and mechanisms of improvement, and suggest multidisciplinary prospective studies of CFS and fatigue in the general population. These studies should pay particular attention to similarities to and differences from functional somatic syndromes and other fatiguing conditions.

Comment in:

Chronic fatigue syndrome. [Lancet. 2006]

Chronic fatigue syndrome. [Lancet. 2006]

 

Source: Prins JB, van der Meer JW, Bleijenberg G. Chronic fatigue syndrome. Lancet. 2006 Jan 28;367(9507):346-55. https://www.ncbi.nlm.nih.gov/pubmed/16443043

 

Diurnal excretion of urinary cortisol, cortisone, and cortisol metabolites in chronic fatigue syndrome

Abstract:

OBJECTIVE: The aim of this study was to obtain comprehensive information on basal hypothalamic-pituitary-adrenal (HPA) axis activity in chronic fatigue syndrome (CFS) patients who were not affected by medication or comorbid psychiatric disorder likely to influence the HPA axis.

METHOD: Steroid analysis of urine collections from 0600 to 2100 h at 3-h intervals in CFS patients and in controls.

RESULTS: Urinary free cortisol and cortisone concentrations showed a significant normal diurnal rhythm, but levels were lower across the cycle in CFS. In contrast, while urinary cortisol metabolites also showed a normal diurnal rhythm, levels were not significantly different between the CFS and controls at any time. Derived metabolite ratios were similar in both groups.

CONCLUSION: This study provides further evidence for reduced basal HPA axis function in patients with CFS, based on lower free cortisol and cortisone levels, but this is not corroborated by cortisol metabolite data. The difference between these measures cannot be explained by an altered timing of the diurnal rhythm.

Comment in: Comment on “diurnal excretion of urinary cortisol, cortisone, and cortisol metabolites in chronic fatigue syndrome”. [J Psychosom Res. 2006]

 

Source: Jerjes WK, Peters TJ, Taylor NF, Wood PJ, Wessely S, Cleare AJ. Diurnal excretion of urinary cortisol, cortisone, and cortisol metabolites in chronic fatigue syndrome. J Psychosom Res. 2006 Feb;60(2):145-53. https://www.ncbi.nlm.nih.gov/pubmed/16439267

 

The management of children with chronic fatigue syndrome-like illness in primary care: a cross-sectional study

Abstract:

BACKGROUND: Most studies on children with chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (ME) have been undertaken in tertiary care and little is known about their management in primary care.

AIM: To describe the characteristics of patients aged 5-19 years with CFS-like illness in primary care and to examine how GPs investigate and manage patients.

DESIGN OF STUDY: Descriptive retrospective questionnaire study.

SETTING: Sixty-two UK GP practices in the MRC General Practice Research Framework (GPRF).

METHOD: One hundred and twenty-two practices were approached; 62 identified 116 patients consulting a GP with severe fatigue lasting over 3 months. Practice nurses and GPs completed questionnaires from medical notes and patients completed postal questionnaires.

RESULTS: Ninety-four patients were considered by a clinical panel, blind to diagnosis, to meet the Oxford CFS criteria with a fatigue duration of 3 months. Seventy-three per cent were girls, 94% white, mean age was 12.9 years and median illness duration 3.3 years. GPs had principal responsibility for 62%. A diagnosis of CFS/ME was made in 55%, 30% of these within 6 months. Fifty per cent had a moderate illness severity. Paediatric referrals were made in 82% and psychiatric referrals in 46% (median time of 2 and 13 months respectively). Advice given included setting activity goals, pacing, rest and graded exercise.

CONCLUSIONS: Patient characteristics are comparable to those reported in tertiary care, although fewer are severe cases. GPs have responsibility for the majority of patients, are diagnosing CFS/ME within a short time and applying a range of referral and advice strategies.

 

Source: Saidi G, Haines L. The management of children with chronic fatigue syndrome-like illness in primary care: a cross-sectional study. Br J Gen Pract. 2006 Jan;56(522):43-7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1821410/ (Full article)

 

Influence of melatonin on fatigue severity in patients with chronic fatigue syndrome and late melatonin secretion

Abstract:

The effect of melatonin, a chronobiotic drug, was explored in 29 patients with chronic fatigue syndrome (CFS) and Dim Light Melatonin onset (DLMO) later than 21.30 hours, reflective of delayed circadian rhythmicity. The patients took 5 mg of melatonin orally, 5 h before DLMO during 3 months.

Their responses to the checklist individual strength (CIS), a reliable questionnaire measuring the severity of personally experienced fatigue, were assessed twice with a 6-week interval immediately before the treatment and once after 3 months treatment.

In the pre-treatment period the fatigue sub-score improved significantly. After treatment, the total CIS score and the sub-scores for fatigue, concentration, motivation and activity improved significantly. The sub-score fatigue normalized in two of the 29 patients in the pre-treatment period and in eight of 27 patients during treatment. This change was significant.

In the patients with DLMO later than 22.00 hours (n=21) the total CIS score and the sub-scores for fatigue, concentration and activity improved significantly more than in the patients (n=8) with DLMO earlier than 22.00 hours. Melatonin may be an effective treatment for patients with CFS and late DLMO, especially in those with DLMO later than 22.00 hours.

 

Source: van Heukelom RO, Prins JB, Smits MG, Bleijenberg G. Influence of melatonin on fatigue severity in patients with chronic fatigue syndrome and late melatonin secretion. Eur J Neurol. 2006 Jan;13(1):55-60. https://www.ncbi.nlm.nih.gov/pubmed/16420393

 

Treatment of chronic fatigue syndrome with antibiotics: pilot study assessing the involvement of Coxiella burnetii infection

Abstract:

OBJECTIVE: To examine whether Coxiella burnetii (C. burnetii) is involved in chronic fatigue syndrome (CFS), we administered tetracycline antibiotics to subjects with CFS, and followed changes in clinical symptoms, PCR findings, and C. burnetii antibody titers.

PATIENTS AND METHODS: The subjects were 8 patients with CFS and 213 with nonspecific complaints such as chronic fatigue and low-grade fever for several months or longer but not meeting the diagnostic criteria for CFS. All were examined for C. burnetii infection by nested PCR and the indirect immunofluorescence test (IF).

RESULTS: Four CFS patients (the CFS group) and 54 controls [the post-Q fever fatigue syndrome (QFS) group] positive for C. burnetii were treated mainly with minocycline or doxycycline (100 mg/day) for 3 months. After treatment, all 58 patients tested negative for C. burnetii infection. In the CFS group, no significant difference was noted between the mean pre- and post-treatment temperatures or headache scores. Similarly, there was no significant improvement in performance status (PS) scores. In the QFS group, however, mean temperatures and headache scores were significantly decreased after treatment (p<0.001). PS scores were also improved.

CONCLUSION: These results suggest the possibility of direct involvement of C. burnetii in the pathological state of CFS to be low, despite the C. burnetii infection rate being high in CFS patients. This is a pilot study and further larger investigations are necessary to confirm our preliminary results.

 

Source: Iwakami E1, Arashima Y, Kato K, Komiya T, Matsukawa Y, Ikeda T, Arakawa Y, Oshida S. Treatment of chronic fatigue syndrome with antibiotics: pilot study assessing the involvement of Coxiella burnetii infection. Intern Med. 2005 Dec;44(12):1258-63. https://www.ncbi.nlm.nih.gov/pubmed/16415546

 

Increase of free Mg2+ in the skeletal muscle of chronic fatigue syndrome patients

Abstract:

In a previous study we evaluated muscle blood flow and muscle metabolism in patients diagnosed with chronic fatigue syndrome (CFS). To better understand muscle metabolism in CFS, we re-evaluated our data to calculate free Magnesium levels in skeletal muscle. Magnesium is an essential cofactor in a number of cell processes. A total of 20 CFS patients and 11 controls were evaluated.

Phosphorus magnetic resonance spectroscopy from the medial gastrocnemius muscle was used to calculate free Mg2+ from the concentrations and chemical shifts of Pi, PCr, and beta ATP peaks. CFS patients had higher magnesium levels in their muscles relative to controls (0.47 + 0.07 vs 0.36 + 0.06 mM, P < 0.01), although there was no difference in the rate of phosphocreatine recovery in these subjects, as reported earlier. This finding was not associated with abnormal oxidative metabolism as measured by the rate of recovery of phosphocreatine after exercise. In summary, calculation of free Mg2+ levels from previous data showed CFS patients had higher resting free Mg2+ levels compared to sedentary controls.

 

Source: McCully KK, Malucelli E, Iotti S. Increase of free Mg2+ in the skeletal muscle of chronic fatigue syndrome patients. Dyn Med. 2006 Jan 11;5:1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1360067/ (Full article)

 

The act of diagnosis: pros and cons of labelling chronic fatigue syndrome

Abstract:

BACKGROUND: One of the many controversies surrounding chronic fatigue syndrome (CFS) is the possible impact of the diagnostic label: is it disabling or enabling? In this paper, we discuss the pros and cons of labelling CFS.

METHOD: A narrative synthesis of the literature.

RESULTS: Diagnosed CFS patients have a worse prognosis than fatigue syndrome patients without such a label. The ways in which CFS patients perceive themselves, label their symptoms and appraise stressors may perpetuate or exacerbate their symptoms, a process that involves psychological, psychosocial and cultural factors. Labels can also lead to conflicts with doctors who fear diagnosis might lead to worse outcomes. However, on the other hand, finding a label that fits one’s condition can provide meaning, emotional relief and recognition, whilst the denial of the diagnosis of CFS in those who have already reached their own conclusion can be very counter productive. The act of diagnosis therefore seems to be a trade-off between empowerment, illness validation and group support, contrasted with the risk of diagnosis as self-fulfilling prophecy of non-recovery.

CONCLUSIONS: The answer to the question of ‘to label or not to label’ may turn out to depend not on the label, but on what that label implies. It is acceptable and often beneficial to make diagnoses such as CFS, provided that this is the beginning, and not the end, of the therapeutic encounter.

 

Source: Huibers MJ, Wessely S. The act of diagnosis: pros and cons of labelling chronic fatigue syndrome. Psychol Med. 2006 Jul;36(7):895-900. Epub 2006 Jan 10. https://www.ncbi.nlm.nih.gov/pubmed/16403245

 

Generalized joint hypermobility is more common in chronic fatigue syndrome than in healthy control subjects

Abstract:

OBJECTIVES: This study aimed at (1) comparing the prevalence of generalized hypermobility in patients with chronic fatigue syndrome (CFS) and healthy volunteers, (2) examining the clinical importance of generalized hypermobility in patients with CFS, and (3) examining whether knee proprioception is associated with hypermobility in patients with CFS.

METHODS: Sixty-eight patients with CFS filled out two self-reported measures (for the assessment of symptom severity and disability), were questioned about muscle and joint pain, and were screened for generalized hypermobility. Afterward, the patients performed a knee repositioning test (assessment of knee proprioception), and it was examined whether or not they fulfilled the criteria for benign joint hypermobility syndrome (BJHS). Sixty-nine age- and sex-matched healthy volunteers were screened for generalized joint hypermobility and performed the same knee repositioning test.

RESULTS: Compared with the healthy volunteers (4.3%, 3/68), significantly more patients with CFS (20.6%, 14/69) fulfilled the criteria for generalized joint hypermobility (Fisher exact test, P < .004). No associations were found between generalized joint hypermobility and the self-reported measures (including pain severity) or knee proprioception (Spearman correlation analysis). Knee proprioception was similar in both groups (Mann-Whitney U = 1961, z = -1.745, P = .81). Forty patients with CFS (58.8%) fulfilled the criteria for BJHS.

CONCLUSIONS: These data indicate that a subgroup of patients with CFS present with generalized joint hypermobility and most patients with of CFS fulfill the diagnostic criteria for BJHS. There appears to be no association between musculoskeletal pain and joint hypermobility in patients with CFS.

 

Source: Nijs J, Aerts A, De Meirleir K. Generalized joint hypermobility is more common in chronic fatigue syndrome than in healthy control subjects. J Manipulative Physiol Ther. 2006 Jan;29(1):32-9. http://www.ncbi.nlm.nih.gov/pubmed/16396727

 

Effect of physical factors on bioelectric properties of cell nuclei of buccal epithelium in students with chronic fatigue syndrome

Abstract:

60 students with the syndrome of chronic fatigue have been observed in a sanatorium. 35 patients of the main (first) group underwent hydrokinesotherapy. The patients of the second group attended physical exercises as follows: girls attended shaping classes and contrast douche, boys exercised on different training apparatus and took too contrast douche. An estimation of efficiency of the carried out treatment was conducted with the help of clinical and paraclinical methods of the study.

Electrokinetic properties of cellular nuclei of buccalium epithelium were tested to reveal a general nonspecific resistance of the human body. The data of assessment of an electrical potential (Z-potential) showed that clinical improvement coincided with the increase in electrokinetic mobility of cell nucleus of buccalium epithelium (P<0.01). Physical factors proved to have positive influence on homeostas of patients of the main group. This index was not reliable in patients of the second group (P>0.5).

 

Source: Samoĭlovych VA, Hutarieva NV, Tondiĭ LD. Effect of physical factors on bioelectric properties of cell nuclei of buccal epithelium in students with chronic fatigue syndrome. Lik Sprava. 2005 Jul-Sep;(5-6):60-4. [Article in Ukrainian] http://www.ncbi.nlm.nih.gov/pubmed/16396296

 

Cognitive dysfunction relates to subjective report of mental fatigue in patients with chronic fatigue syndrome

Abstract:

Patients with chronic fatigue syndrome (CFS) frequently complain of cognitive dysfunction. However, evidence of cognitive impairment in CFS patients has been found in some, but not other, studies. This heterogeneity in findings may stem from the relative presence of mental fatigue in the patient populations examined. The present study assessed this possibility in a population-based sample of CFS patients.

In all, 43 patients with CFS defined by the criteria of the 1994 research case definition using measurements recommended by the 2003 International CFS Study Group, and 53 age-, sex-, and race/ethnicity-matched nonfatigued subjects were included in the study. Mental fatigue was assessed using the mental fatigue subscale of the multidimensional fatigue inventory. Cognitive function was evaluated using an automated battery of computerized tests (Cambridge neuropsychological test automated battery (CANTAB)) that assessed psychomotor function, planning and problem-solving abilities, and memory and attentional performance.

CFS patients with significant complaints of mental fatigue (score of mental fatigue 2 standard deviations above the mean of nonfatigued subjects) exhibited significant impairment in the spatial working memory and sustained attention (rapid visual information processing) tasks when compared to CFS patients with low complaints of mental fatigue and nonfatigued subjects. In CFS patients with significant mental fatigue, sustained attention performance was impaired only in the final stages of the test, indicating greater cognitive fatigability in these patients. CFS patients with low mental fatigue displayed performance comparable to nonfatigued subjects on all tests of the CANTAB battery. These findings show strong concordance between subjective complaints of mental fatigue and objective measurement of cognitive impairment in CFS patients and suggest that mental fatigue is an important component of CFS-related cognitive dysfunction.

 

Source: Capuron L, Welberg L, Heim C, Wagner D, Solomon L, Papanicolaou DA, Craddock RC, Miller AH, Reeves WC. Cognitive dysfunction relates to subjective report of mental fatigue in patients with chronic fatigue syndrome. Neuropsychopharmacology. 2006 Aug;31(8):1777-84. Epub 2006 Jan 4. http://www.nature.com/npp/journal/v31/n8/full/1301005a.html (Full article)