Tag: 2006

Challenges for molecular profiling of chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is prevalent, disabling and costly. Despite extensive literature describing the epidemiology and clinical aspects of CFS, it has been recalcitrant to diagnostic biomarker discovery and therapeutic intervention. This is due to the fact that CFS is a complex illness defined by self-reported symptoms and diagnosed by the exclusion of medical and psychiatric diseases that may explain the symptoms.

Studies attempting to dissect the pathophysiology are challenging to design as CFS affects multiple body systems, making the choice of which system to study dependent on an investigators area of expertise. However, the peripheral blood appears to be facilitating the molecular profiling of several diseases, such as CFS, that involve bodywide perturbations that are mediated by the CNS. Successful molecular profiling of CFS will require the integration of genetic, genomic and proteomic data with environmental and behavioral data to define the heterogeneity in order to optimize intervention.

 

Source: Vernon SD, Whistler T, Aslakson E, Rajeevan M, Reeves WC. Challenges for molecular profiling of chronic fatigue syndrome. Pharmacogenomics. 2006 Mar;7(2):211-8. https://www.ncbi.nlm.nih.gov/pubmed/16515400

 

Reduced responsiveness is an essential feature of chronic fatigue syndrome: a fMRI study

Abstract:

BACKGROUND: Although the neural mechanism of chronic fatigue syndrome has been investigated by a number of researchers, it remains poorly understood.

METHODS: Using functional magnetic resonance imaging, we studied brain responsiveness in 6 male chronic fatigue syndrome patients and in 7 age-matched male healthy volunteers. Responsiveness of auditory cortices to transient, short-lived, noise reduction was measured while subjects performed a fatigue-inducing continual visual search task.

RESULTS: Responsiveness of the task-dependent brain regions was decreased after the fatigue-inducing task in the normal and chronic fatigue syndrome subjects and the decrement of the responsiveness was equivalent between the 2 groups. In contrast, during the fatigue-inducing period, although responsiveness of auditory cortices remained constant in the normal subjects, it was attenuated in the chronic fatigue syndrome patients. In addition, the rate of this attenuation was positively correlated with the subjective sensation of fatigue as measured using a fatigue visual analogue scale, immediately before the magnetic resonance imaging session.

CONCLUSION: Chronic fatigue syndrome may be characterised by attenuation of the responsiveness to stimuli not directly related to the fatigue-inducing task.

 

Source: Tanaka M, Sadato N, Okada T, Mizuno K, Sasabe T, Tanabe HC, Saito DN, Onoe H, Kuratsune H, Watanabe Y. BMC Neurol. 2006 Feb 22;6:9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1397862/ (Full article)

 

How relevant are exercise capacity measures for evaluating treatment effects in chronic fatigue syndrome? Results from a prospective, multidisciplinary outcome study

Abstract:

OBJECTIVE: To evaluate the outcome of a multidisciplinary treatment programme for patients with chronic fatigue syndrome, including health-related quality of life (HRQoL) and psychosocial variables, and exercise capacity measures.

DESIGN: A six-month prospective outcome study.

SETTING: University outpatient rehabilitation clinic; group setting.

SUBJECTS: One hundred and sixteen women fulfilling chronic fatigue syndrome criteria.

INTERVENTIONS: Cognitive behaviourally and graded exercise-based strategies; emphasis on adaptive lifestyle changes.

MEASURES: Short Form General Health Survey (SF-36); Symptom Checklist (SCL-90); Causal Attribution List (CAL); Self-Efficacy Scale (SE); maximum progressive bicycle ergometer test with respiratory gas analysis; and isokinetic leg strength test, before and after treatment.

RESULTS: The total group significantly improved on nearly all reported HRQoL/psychosocial variables. Changes in exercise capacity measures were rather modest and did not correlate or only weakly correlated with HRQoL/psychosocial variables. Subgroup analyses indicated that less fit patients improved significantly more on exercise capacity measures than their more fit counterparts. Patients who were fitter at baseline scored better on pretreatment HRQoL/psychosocial variables, but both subgroups improved similarly on these variables.

CONCLUSIONS: Health-related quality of life and psychosocial functioning in patients with chronic fatigue syndrome improves after a six-month cognitive behaviourally and graded exercise-based multidisciplinary treatment programme. Increase in exercise capacity measures is not a necessary condition for reported improvements, except for less fit patients.

 

Source: Pardaens K, Haagdorens L, Van Wambeke P, Van den Broeck A, Van Houdenhove B. How relevant are exercise capacity measures for evaluating treatment effects in chronic fatigue syndrome? Results from a prospective, multidisciplinary outcome study. Clin Rehabil. 2006 Jan;20(1):56-66. https://www.ncbi.nlm.nih.gov/pubmed/16502751

 

Patients with chronic fatigue syndrome have reduced absolute cortical blood flow

Abstract:

Prior studies on brain blood flow in chronic fatigue syndrome (CFS) did not find consistent results. This may be because they used single-photon emission computed tomography to measure brain blood flow, which could not measure absolute blood flow. Therefore, the aim of this study was to test the hypothesis that patients with CFS have reduced absolute cerebral blood flow. Xenon-computed tomography blood flow studies were done on 25 CFS patients and seven healthy controls. Analyses were done after stratifying the CFS patients based on the presence or absence of a current psychiatric disorder.

Flow was diminished in both groups as follows: patients with no current psychiatric disorders had reduced cortical blood flow in the distribution of both right and left middle cerebral arteries (P<0.05 for both) while those with current psychiatric disorders had reduced blood flow only in the left middle cerebral artery territory (P<0.05). These data indicate that patients with CFS have reduced absolute cortical blood flow in rather broad areas when compared with data from healthy controls and that those devoid of psychopathology had the most reductions in cortical flow. These data support, in part, our earlier findings that patients devoid of psychopathology are the group most at risk of having some of the symptoms of CFS due to brain dysfunction.

 

Source: Yoshiuchi K, Farkas J, Natelson BH. Patients with chronic fatigue syndrome have reduced absolute cortical blood flow. Clin Physiol Funct Imaging. 2006 Mar;26(2):83-6. https://www.ncbi.nlm.nih.gov/pubmed/16494597

 

Is chronic fatigue syndrome associated with platelet activation?

Abstract:

Chronic fatigue syndrome (CFS) is a debilitating condition that has no known aetiology or pathophysiology. Recent investigations by other workers have suggested that individuals with CFS may have a hypercoagulable state. This study investigated various aspects of platelet activation and function in 17 patients with CFS and in 16 age-matched and sex-matched healthy controls. Platelet aggregation, platelet volume and coagulation tests were performed.

Platelet aggregation was investigated by means of the photometric changes using citrated platelet-rich plasma, whole blood aggregation was calculated as the percentage fall in single platelet counts and the coagulation tests were performed on an automatic microcentrifugal analyser.A trend was observed for the patients to have lower aggregation results and a reduced mean platelet volume. However, this only reached statistical significance for one result; the rate of the aggregation slope by 1.0 microg/ml collagen [CFS patients, 18 (9-28) versus controls, 32.5 (19-36); Mann-Whitney U test, P = 0.029].

No significant differences were found for any of the measurements of coagulation. These results are in contrast to previously reported findings. However, due to the heterogeneous nature of the disease, and the resulting lifestyles of the patients, caution should be taken when comparing one group of patients with another. Nevertheless, we certainly found no evidence of increased platelet activation or of a hypercoagulable state in patients with CFS and, on the basis of these results, anti-platelet or anti-coagulant therapy is not warranted.

 

Source: Kennedy G, Norris G, Spence V, McLaren M, Belch JJ. Is chronic fatigue syndrome associated with platelet activation? Blood Coagul Fibrinolysis. 2006 Mar;17(2):89-92. https://www.ncbi.nlm.nih.gov/pubmed/16479189

 

Sub-typing CFS patients on the basis of ‘minor’ symptoms

Abstract:

The diagnosis of chronic fatigue syndrome (CFS), an illness characterized by medically unexplained fatigue, depends on a clinical case definition representing one or more pathophysiological mechanisms. To prepare for studies of these mechanisms, this study sought to identify subtypes of CFS.

In 161 women meeting 1994 criteria for CFS, principal components analysis of the 10 ‘minor’ symptoms of CFS produced three factors interpreted to indicate musculoskeletal, infectious and neurological subtypes. Extreme scores on one or more of these factors characterized about 2/3 of the sample. Those characterized by the neurological factor were at increased risk of reduced scores on cognitive tests requiring attention, working memory, long-term memory or rapid performance.

In addition, the neurological subtype was associated with reduced levels of function. Those characterized by the musculoskeletal factor were at increased risk for the diagnosis of fibromyalgia (chronic widespread pain and mechanical allodynia) and reduced physical function. Those characterized by the infectious factor were less likely to evidence co-occurring fibromyalgia, and showed lesser risk of functional impairment.

The prevalence of disability was increased in those with the highest scores on any of the subtypes, as well as in those with high scores on multiple factors. Depression and anxiety, while frequently present, were not more prevalent in any particular subtype, and did not increase with the severity of specific symptom reports. Results suggest that subtypes of CFS may be identified from reports of the minor diagnostic symptoms, and that these subtypes demonstrate construct validity.

 

Source: Janal MN, Ciccone DS, Natelson BH. Sub-typing CFS patients on the basis of ‘minor’ symptoms. Biol Psychol. 2006 Aug;73(2):124-31. Epub 2006 Feb 10. https://www.ncbi.nlm.nih.gov/pubmed/16473456

 

Does methylphenidate reduce the symptoms of chronic fatigue syndrome?

Abstract:

PURPOSE: Chronic fatigue syndrome is a clinical entity consisting of prolonged and debilitating fatigue in which concentration disturbances are very frequent. Until now, no medical treatment has shown any efficacy. The objectives of this study were to investigate the short-term effects of methylphenidate, an amphetamine derivative, on fatigue, concentration disturbances, and quality of life.

SUBJECTS AND METHODS: A double-blind randomized placebo-controlled crossover study was conducted in 60 patients who fulfilled the 1994 Centers for Disease Control criteria for chronic fatigue syndrome and had concentration difficulties. Patients were enrolled between March 2003 and March 2004 at the outpatient department of a university hospital referral center for chronic fatigue syndrome patients. Random assignment to 4 weeks treatment with methylphenidate 2 x 10 mg/day, followed by 4 weeks of placebo treatment, or 4 weeks of placebo treatment, followed by methylphenidate treatment. Fatigue and concentration were measured with a Checklist Individual Strength (CIS) and a Visual Analogue Scale (VAS).

RESULTS: Fatigue scores fell significantly during methylphenidate intake in comparison with baseline (mean difference: -0.7, P = .010 for VAS; mean difference: -11.8, P <.0001 for CIS) and in comparison with placebo (mean difference: -1.0, P = .001 for VAS; mean difference: -9.7, P <.0001 for CIS). Concentration disturbances, measured with a VAS improved significantly under methylphenidate treatment compared with baseline (mean difference: -1.3, P <.0001) and compared with placebo (mean difference: -1.1, P <.0001). A clinical significant effect (> or =33% improvement or CIS < or =76) on fatigue was achieved in 17% of patients, who were considered responders; on concentration in 22% of patients.

CONCLUSIONS: Methylphenidate at a dose of 2 x 10 mg/day is significantly better than placebo in relieving fatigue and concentration disturbances in a minority of chronic fatigue syndrome patients. Further studies are needed to investigate the long-term effects of this treatment.

 

Source: Blockmans D, Persoons P, Van Houdenhove B, Bobbaers H. Does methylphenidate reduce the symptoms of chronic fatigue syndrome? Am J Med. 2006 Feb;119(2):167.e23-30. https://www.ncbi.nlm.nih.gov/pubmed/16443425

 

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)