LPS-induced IL-10 production in whole blood cultures from chronic fatigue syndrome patients is increased but supersensitive to inhibition by dexamethasone

Abstract:

Several causes have been held responsible for the chronic fatigue syndrome (CFS), including an altered hypothalamus-pituitary-adrenal gland (HPA)-axis activity, viral infections and a reduced Th1 activity. Therefore, it was investigated whether the regulation of IL-10 is different in CFS.

LPS-induced cytokine secretion in whole blood cultures showed a significant increase in IL-10 and a trend towards a decrease in IL-12 as compared with healthy controls. In patients and controls, IL-12 secretion was equally sensitive to suppression by dexamethasone, whereas IL-10 secretion appeared more sensitive in CFS-patients. In controls, IL-10 and IL-12 secretion were inversely correlated with free serum cortisol (r=-0.492, p<0.02 and r=-0.434, p<0.05, respectively). In CFS, such an inverse correlation was found for IL-12 (r=-0.611, p<0.02) but not for IL-10 (r=-0.341, ns).

These data are suggestive for a disturbed glucocorticoid regulation of IL-10 in CFS.

 

Source: Visser J, Graffelman W, Blauw B, Haspels I, Lentjes E, de Kloet ER, Nagelkerken L. LPS-induced IL-10 production in whole blood cultures from chronic fatigue syndrome patients is increased but supersensitive to inhibition by dexamethasone. J Neuroimmunol. 2001 Oct 1;119(2):343-9. http://www.ncbi.nlm.nih.gov/pubmed/11585638

 

Cardiovascular responses of women with chronic fatigue syndrome to stressful cognitive testing before and after strenuous exercise

Abstract:

OBJECTIVE: The purpose of this study was to compare the cardiovascular responses of patients with chronic fatigue syndrome (CFS) to healthy control subjects when performing stressful cognitive tasks before and after strenuous exercise.

METHOD: Beat-by-beat blood pressure and electrocardiogram were recorded on 19 women with CFS and 20 healthy nonexercising (ie, sedentary) women while they performed cognitive tests before, immediately after, and 24 hours after incremental exercise to exhaustion.

RESULTS: Diminished heart rate (p <.01) and systolic (p <.01) and diastolic (p <.01) blood pressure responses to stressful cognitive testing were seen in patients with CFS when compared with healthy, sedentary controls. This diminished stress response was seen consistently in patients with CFS across three separate cognitive testing sessions. Also, significant negative correlations between self-ratings of CFS symptom severity and cardiovascular responses were seen (r = -0.62, p <.01).

CONCLUSIONS: Women with CFS have a diminished cardiovascular response to cognitive stress; however, exercise did not magnify this effect. Also, the data showed that the patients with the lowest cardiovascular reactivity had the highest ratings of CFS symptom severity, which suggests that the individual response of the patient with CFS to stress plays a role in the common complaint of symptoms worsening after stress.

 

Source: LaManca JJ, Peckerman A, Sisto SA, DeLuca J, Cook S, Natelson BH. Cardiovascular responses of women with chronic fatigue syndrome to stressful cognitive testing before and after strenuous exercise. Psychosom Med. 2001 Sep-Oct;63(5):756-64. http://www.ncbi.nlm.nih.gov/pubmed/11573024

 

Corticospinal inhibition appears normal in patients with chronic fatigue syndrome

Abstract:

The pathogenesis of chronic fatigue syndrome (CFS) remains unknown. Thresholds and latencies of motor evoked potentials (MEPs) in response to transcranial magnetic stimulation (TMS) are normal but intracortical inhibition has not been investigated.

Eleven patients with CFS were compared with 11 control subjects. Each patient completed a questionnaire using visual analogue indices of pain, fatigue, anxiety and depression. Subjects released a button to initiate simple (SRTs) and choice reaction time (CRTs) tasks; for each task, movement times were measured between release of the initiation button and depression of a second button 15 cm away. Subjects held a 10 % maximum voluntary contraction in the thenar muscles of their dominant hand while TMS was applied to the motor cortex; the duration and extent of inhibition of surface electromyographic (EMG) activity were assessed at stimulus strengths above and below the threshold for MEPs.

Patients had significantly (P < 0.05) higher mean indices of fatigue than of pain, anxiety or depression. Mean (+/- S.E.M.) SRTs (but not CRTs) were longer in patients (309 +/- 45 ms) than in controls (218 +/- 9 ms). Movement times were longer in patients for both SRTs and CRTs. TMS thresholds, expressed as a percentage of the maximum stimulator output, were not significantly (P > 0.05) different in both groups for both MEPs (patients, 34 +/- 3%; controls, 36 +/- 3%) and inhibition of voluntary contraction (patients, 29 +/- 2%; controls, 34 +/- 4%). The duration and extent of inhibition did not differ significantly between groups at any stimulus strength. The pattern of change in duration and extent of inhibition with increasing stimulus intensity was no different in the two groups. The duration and extent of corticospinal inhibition in patients with CFS did not differ from controls, adding further evidence to the notion that the feeling of fatigue and the slowness of movement seen in CFS is not manifest in corticospinal output pathways.

 

Source: Zaman R, Puri BK, Main J, Nowicky AV, Davey NJ. Corticospinal inhibition appears normal in patients with chronic fatigue syndrome. Exp Physiol. 2001 Sep;86(5):547-50. http://www.ncbi.nlm.nih.gov/pubmed/11571481

 

IgE levels are the same in chronic fatigue syndrome (CFS) and control subjects when stratified by allergy skin test results and rhinitis types

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) has an uncertain pathogenesis. Allergies have been suggested as one cause.

OBJECTIVE: The aim of this study was to compare serum immunoglobulin (Ig)E in CFS and control subjects to determine whether IgE levels were elevated in CFS. This would be suggestive of increased atopy in CFS.

METHODS: IgE was measured by quantitative ELISA (sandwich) immunoassay in 95 CFS and 109 non-CFS control subjects. Subjects were classified by positive or negative allergy skin tests (AST) and rhinitis questionnaires (rhinitis score, RhSc) into four rhinitis types: nonallergic rhinitis (NAR with positive RhSc and negative AST); allergic rhinitis (AR with positive AST and RhSc); atopic/no rhinitis (AST positive/RhSc negative); and nonatopic/no rhinitis (both AST and RhSc negative) subjects.

RESULTS: IgE was not significantly different between control (128 +/- 18 IU/mL, mean +/- SEM) and CFS (133 +/- 43 IU/mL) groups, or between control and CFS groups classified into the four rhinitis types. IgE was significantly higher in subjects with positive AST whether or not they had positive RhSc or CFS symptoms.

CONCLUSIONS: Elevated IgE and positive AST indicate allergen sensitization, but are not necessarily indicators of symptomatic allergic diseases. There was no association between IgE levels and CFS, indicating that atopy was probably not more prevalent in CFS. Therefore, TH2-lymphocyte and IgE-mast cell mechanisms are unlikely causes of CFS.

 

Source: Repka-Ramirez MS, Naranch K, Park YJ, Velarde A, Clauw D, Baraniuk JN. IgE levels are the same in chronic fatigue syndrome (CFS) and control subjects when stratified by allergy skin test results and rhinitis types. Ann Allergy Asthma Immunol. 2001 Sep;87(3):218-21. http://www.ncbi.nlm.nih.gov/pubmed/11570618

 

Chronic fatigue syndrome (CFS) associated with Staphylococcus spp. bacteremia, responsive to potassium arsenite 0.5% in a veterinary surgeon and his coworking wife, handling with CFS animal cases

Abstract:

Chronic fatigue syndrome (CFS) in human patients remain a controversial and perplexing condition with emerging zoonotic aspects. Recent advances in human medicine seem to indicate a bacterial etiology and the condition has already been described in horses, dogs, cats and birds of prey in association with micrococci-like organisms in the blood.

To evaluate the possibility of a chronic bacteremia, a veterinary surgeon (the author) and his coworking wife, both diagnosed with CFS and meeting the CDC working case definition, were submitted to rapid blood cultures and fresh blood smears investigations.

Blood cultures proved Staph-positive and micrococci-like organisms in the blood were repeatedly observed in the 3-year period preceding the arsenical therapy, during which several medicaments, including antibiotics, proved unsuccessful. Following treatment with a low dosage arsenical drug (potassium arsenite 0.5%, im., 1 ml/12 h, for 10 days) both patients experienced complete remission. At the post-treatment control made 1 month later, micrococci had disappeared from the blood, and the CD4/CD8 ratio was raising.

 

Source: Tarello W. Chronic fatigue syndrome (CFS) associated with Staphylococcus spp. bacteremia, responsive to potassium arsenite 0.5% in a veterinary surgeon and his coworking wife, handling with CFS animal cases. Comp Immunol Microbiol Infect Dis. 2001 Oct;24(4):233-46. http://www.ncbi.nlm.nih.gov/pubmed/11561958

 

Interventions for the treatment and management of chronic fatigue syndrome: a systematic review

Erratum in: JAMA 2002 Mar 20;287(11):1401.

Abstract:

CONTEXT: A variety of interventions have been used in the treatment and management of chronic fatigue syndrome (CFS). Currently, debate exists among health care professionals and patients about appropriate strategies for management.

OBJECTIVE: To assess the effectiveness of all interventions that have been evaluated for use in the treatment or management of CFS in adults or children.

DATA SOURCES: Nineteen specialist databases were searched from inception to either January or July 2000 for published or unpublished studies in any language. The search was updated through October 2000 using PubMed. Other sources included scanning citations, Internet searching, contacting experts, and online requests for articles.

STUDY SELECTION: Controlled trials (randomized or nonrandomized) that evaluated interventions in patients diagnosed as having CFS according to any criteria were included. Study inclusion was assessed independently by 2 reviewers. Of 350 studies initially identified, 44 met inclusion criteria, including 36 randomized controlled trials and 8 controlled trials.

DATA EXTRACTION: Data extraction was conducted by 1 reviewer and checked by a second. Validity assessment was carried out by 2 reviewers with disagreements resolved by consensus. A qualitative synthesis was carried out and studies were grouped according to type of intervention and outcomes assessed.

DATA SYNTHESIS: The number of participants included in each trial ranged from 12 to 326, with a total of 2801 participants included in the 44 trials combined. Across the studies, 38 different outcomes were evaluated using about 130 different scales or types of measurement. Studies were grouped into 6 different categories. In the behavioral category, graded exercise therapy and cognitive behavioral therapy showed positive results and also scored highly on the validity assessment. In the immunological category, both immunoglobulin and hydrocortisone showed some limited effects but, overall, the evidence was inconclusive. There was insufficient evidence about effectiveness in the other 4 categories (pharmacological, supplements, complementary/alternative, and other interventions).

CONCLUSIONS: Overall, the interventions demonstrated mixed results in terms of effectiveness. All conclusions about effectiveness should be considered together with the methodological inadequacies of the studies. Interventions which have shown promising results include cognitive behavioral therapy and graded exercise therapy. Further research into these and other treatments is required using standardized outcome measures.

Comment in:

Measuring the quality of trials of treatments for chronic fatigue syndrome. [JAMA. 2001]

Chronic fatigue syndrome–trials and tribulations. [JAMA. 2001]

Review: behavioural interventions show the most promise for chronic fatigue syndrome. [Evid Based Nurs. 2002]

Review: behavioral interventions show the most promise for the chronic fatigue syndrome. [ACP J Club. 2002]

Review: cognitive behavioural therapy and graded exercise show the most promise for chronic fatigue syndrome. [Evid Based Ment Health. 2002]

 

Source: Whiting P, Bagnall AM, Sowden AJ, Cornell JE, Mulrow CD, Ramírez G. Interventions for the treatment and management of chronic fatigue syndrome: a systematic review. JAMA. 2001 Sep 19;286(11):1360-8. http://www.ncbi.nlm.nih.gov/pubmed/11560542

 

A definition-based analysis of symptoms in a large cohort of patients with chronic fatigue syndrome

Abstract:

OBJECTIVE: The Holmes and Fukuda criteria are widely used criteria all over the world, yet a specific European study regarding chronic fatigue syndrome (CFS) patient symptomatology has not been conducted so far. This study was performed to answer the need to assess the homogeneity of a large CFS population in relationship to the Fukuda or Holmes definitions and to assess the importance of a symptom severity scale.

DESIGN: Multivariate analyses were performed to assess the symptom presentation within a fatigued population and the differences between the Fukuda and Holmes definitions compared with an excluded chronic fatigued group in a large cohort of fatigued patients.

SETTING: An outpatient tertiary care setting fatigue clinic in Brussels.

MAIN OUTCOME MEASURES: Prevalence and severity of symptoms and signs in a CFS population and in a chronic fatigued population.

SUBJECTS AND METHODS: A total of 2073 consecutive patients with major complaints of prolonged fatigue participated in this study. Multivariate analyses were performed to assess the symptom presentation and severity and the differences between the Fukuda and Holmes definitions.

RESULTS: Of the 2073 patients complaining of chronic fatigue (CF), 1578 CFS patients fulfilled the Fukuda criteria (100% of CFS group) and 951 (60.3% of the CFS group) fulfilled the Holmes criteria. Discriminant function analysis revealed that the Fukuda and Holmes definitions can be differentiated by symptom severity and prevalence. The Holmes definition was more strongly associated than the Fukuda definition with the symptoms that differentiated the CFS patients from the patients that did not comply with the CFS definitions. The inclusion of 10 additional symptoms was found to improve the sensitivity/specificity and accuracy for selection of CFS patients.

CONCLUSIONS: The CFS patients fulfilling the Holmes criteria have an increased symptom prevalence and severity of many symptoms. Patients fulfilling the Fukuda criteria were less severely affected patients which leads to an increase in clinical heterogeneity. Addition of certain symptoms and removal of others would strengthen the ability to select CFS patients.

 

Source: De Becker P, McGregor N, De Meirleir K. A definition-based analysis of symptoms in a large cohort of patients with chronic fatigue syndrome. J Intern Med. 2001 Sep;250(3):234-40. http://onlinelibrary.wiley.com/doi/10.1046/j.1365-2796.2001.00890.x/full (Full article)

 

What is chronic fatigue syndrome? Heterogeneity within an international multicentre study

Abstract:

OBJECTIVE: We sought to compare the characteristics of patients presenting with chronic fatigue (CF) and related syndromes in eight international centres and to subclassify these subjects based on symptom profiles. The validity of the subclasses was then tested against clinical data.

METHOD: Subjects with a clinical diagnosis of CF completed a 119-item self-report questionnaire to provide clinical symptom data and other information such as illness course and functional impairment. Subclasses were generated using a principal components-like analysis followed by latent profile analysis (LPA).

RESULTS: 744 subjects returned complete data sets (mean age 40.8 years, mean length of illness 7.9 years, female to male ratio 3:1). Overall, the subjects had a high rate of reporting typical CF symptoms (fatigue, neuropsychological dysfunction, sleep disturbance). Using LPA, two subclasses were generated. Class one (68% sample) was characterized by: younger age, lower female to male ratio; shorter episode duration; less premorbid, current and familial psychiatric morbidity; and, less functional disability. Class two subjects (32%) had features more consistent with a somatoform illness. There was substantial variation in subclass prevalences between the study centres (Class two range 6-48%).

CONCLUSIONS: Criteria-based approaches to the diagnosis of CF and related syndromes do not select a homogeneous patient group. While substratification of patients is essential for further aetiological and treatment research, the basis for allocating such subcategories remains controversial.

 

Source: Wilson A, Hickie I, Hadzi-Pavlovic D, Wakefield D, Parker G, Straus SE, Dale J, McCluskey D, Hinds G, Brickman A, Goldenberg D, Demitrack M, Blakely T,Wessely S, Sharpe M, Lloyd A. What is chronic fatigue syndrome? Heterogeneity within an international multicentre study. Aust N Z J Psychiatry. 2001 Aug;35(4):520-7. http://www.ncbi.nlm.nih.gov/pubmed/11531735

 

A comparison of individual and family psychology of adolescents with chronic fatigue syndrome, rheumatoid arthritis, and mood disorders

Abstract:

Chronic fatigue syndrome (CFS) is a controversial diagnosis with unknown cause. Adult studies indicate high rates of psychosocial dysfunction and psychiatric comorbidity. The authors compared three groups of pediatric patients selected by diagnosis-(1l) CFS (n = 15), (2) juvenile rheumatoid arthritis (n = 15), and (3) mood disorders (n = 15)-across many psychological measures.

CFS subjects had dramatic elevation of the Somatic Complaints subscale (mean T score = 75), whereas the mood disorders group had higher externalizing scores (mean T score = 68) on the Child Behavior Checklist. The CFS subjects missed significantly more school compared with the two control groups. After the onset of CFS, 13 of 15 of the CFS patients required significant educational accommodation. Only 4 of the 15 CFS patients had an Axis I psychiatric diagnosis, as determined by the Computerized Diagnostic Interview for Children.

Despite a low rate of psychiatric diagnosis in the CFS sample, these data attest to their psychosocial and school dysfunction.

 

Source: Gray D, Parker-Cohen NY, White T, Clark ST, Seiner SH, Achilles J, McMahon WM. A comparison of individual and family psychology of adolescents with chronic fatigue syndrome, rheumatoid arthritis, and mood disorders. J Dev Behav Pediatr. 2001 Aug;22(4):234-42. http://www.ncbi.nlm.nih.gov/pubmed/11530896

 

Intraindividual variability in cognitive performance in persons with chronic fatigue syndrome

Abstract:

Studies of cognitive performance among persons with chronic fatigue syndrome (CFS) have yielded inconsistent results. We sought to contribute to findings in this area by examining intraindividual variability as well as level of performance in cognitive functioning.

A battery of cognitive measures was administered to 14 CFS patients and 16 healthy individuals on 10 weekly occasions. Analyses comparing the two groups in terms of level of performance defined by latency and accuracy scores revealed that the CFS patients were slower but not less accurate than healthy persons.

The CFS group showed greater intraindividual variability (as measured by intraindividual standard deviations and coefficients of variation) than the healthy group, although the results varied by task and time frame. Intraindividual variability was found to be stable across time and correlated across tasks at each testing occasion. Intraindividual variability also uniquely differentiated the groups. The present findings support the proposition that intraindividual variability is a meaningful indicator of cognitive functioning in CFS patients.

 

Source: Fuentes K, Hunter MA, Strauss E, Hultsch DF. Intraindividual variability in cognitive performance in persons with chronic fatigue syndrome. Clin Neuropsychol. 2001 May;15(2):210-27. http://www.ncbi.nlm.nih.gov/pubmed/11528543