Sympathetic cardiovascular control during orthostatic stress and isometric exercise in adolescent chronic fatigue syndrome

Abstract:

The chronic fatigue syndrome (CFS) has been shown to be associated with orthostatic intolerance and cardiovascular dysregulation. We investigated the cardiovascular responses to combined orthostatic stress and isometric exercise in adolescents with CFS.

We included a consecutive sample of 15 adolescents 12-18 years old with CFS diagnosed according to a thorough and standardized set of investigations, and a volunteer sample of 56 healthy control subjects of equal sex and age distribution. Heart rate, systolic, mean and diastolic blood pressure, stroke index, and total peripheral resistance index were non-invasively recorded during lower body negative pressure (LBNP) combined with two consecutive periods of handgrip. In addition, we measured baseline plasma catecholamines, and recorded symptoms. At rest, CFS patients had higher heart rate, diastolic blood pressure, plasma norepinephrine (P < 0.01), mean blood pressure and plasma epinephrine (P < 0.05) than controls.

During LBNP, CFS patients had a greater increase in heart rate, diastolic blood pressure, mean blood pressure (P < 0.05) and total peripheral resistance index (n.s.) than controls. During handgrip, CFS patients had a smaller increase in heart rate, diastolic blood pressure (P < 0.05), mean blood pressure and total peripheral resistance index (n.s.) than controls.

Our results indicate that adolescents with CFS have increased sympathetic activity at rest with exaggerated cardiovascular response to orthostatic stress, but attenuated cardiovascular response when performing isometric exercise during orthostatic stress. This suggests that CFS might be causally related to sympathetic dysfunction.

 

Source: Wyller VB, Saul JP, Walløe L, Thaulow E. Sympathetic cardiovascular control during orthostatic stress and isometric exercise in adolescent chronic fatigue syndrome. Eur J Appl Physiol. 2008 Apr;102(6):623-32. Epub 2007 Dec 8. https://www.ncbi.nlm.nih.gov/pubmed/18066580

 

Increased serum IgM antibodies directed against phosphatidyl inositol (Pi) in chronic fatigue syndrome(CFS) and major depression: evidence that an IgM-mediated immune response against Pi is one factor underpinning the comorbidity between both CFS and depression

Abstract:

Major depression and chronic fatigue syndrome (CFS) are accompanied by signs of oxidative and nitrosative stress (O&NS) and an inflammatory response. Phosphatidyl inositol (Pi) is thought to play a role in depression. The aim of the present study is to examine whether depression and CFS are characterized by an IgM-mediated immune response directed against Pi. Toward this end, this study examines the serum IgM antibodies directed against Pi in 14 patients with major depression, 14 patients with CFS, 14 subjects with partial CFS, and in 11 normal controls.

We found that the prevalence and mean value for the serum IgM levels directed against Pi were significantly greater in patients with major depression and CFS than in normal controls and patients with partial CFS. There were significant and positive correlations between serum IgM levels directed against Pi and two symptoms of the FibroFatigue Scale, i.e. fatigue and depression.

The results show that an IgM-related immune response directed against Pi may occur in both depression and CFS and may play a role in the pathophysiology of the key symptom of CFS and major depression. It is suggested that the above disorders in Pi result from increased O&NS in both depression and CFS. Autoanti-Pi antibodies may have biological effects, for example, by changing inositol 1,4,5-triphosphate (IP3), phosphatidylinositol-4,5-bisphosphate (PIP2), diacylglycerol and phosphatidylinositol-3,4,5-triphosphate (PIP3) production, thus interfering with intracellular signalling processes. Future research in major depression and CFS should focus on the functional consequences of the immune responses directed against Pi.

 

Source: Maes M, Mihaylova I, Leunis JC. Increased serum IgM antibodies directed against phosphatidyl inositol (Pi) in chronic fatigue syndrome(CFS) and major depression: evidence that an IgM-mediated immune response against Pi is one factor underpinning the comorbidity between both CFS and depression. Neuro Endocrinol Lett. 2007 Dec;28(6):861-7. https://www.ncbi.nlm.nih.gov/pubmed/18063934

 

Normalization of the increased translocation of endotoxin from gram negative enterobacteria (leaky gut) is accompanied by a remission of chronic fatigue syndrome

Abstract:

There is now evidence that chronic fatigue syndrome (CFS) is accompanied by an increased translocation of endotoxins from gram-negative enterobacteria through the gut wall, as demonstrated by increased prevalences and median values for serum IgM and IgA against the endotoxins of gram-negative enterobacteria. This condition can also be described as increased gut permeability or leaky gut and indicates intestinal mucosal dysfunction (IMD).

Here we report a case of a 13 year old girl with CFS who showed very high values for serum IgM against the LPS of some enterobacteria and signs of oxidative and nitrosative stress, activation of the inflammatory response system, and IgG3 subclass deficiency. Upon treatment with specific antioxidants and a “leaky gut diet”, which both aim to treat increased gut permeability, and immunoglobins intravenously, the increased translocation of the LPS of gram negative enterobacteria normalized and this normalization was accompanied by a complete remission of the CFS symptoms.

 

Source: Maes M, Coucke F, Leunis JC. Normalization of the increased translocation of endotoxin from gram negative enterobacteria (leaky gut) is accompanied by a remission of chronic fatigue syndrome. Neuro Endocrinol Lett. 2007 Dec;28(6):739-44. https://www.ncbi.nlm.nih.gov/pubmed/18063928

 

Efficacy of cognitive behavioral therapy for chronic fatigue syndrome: a meta-analysis

Abstract:

A meta-analysis of the efficacy of cognitive behavioral therapy (CBT) in treating chronic fatigue included 15 effect sizes for between-group outcome comparisons. Across analyses, which included a total of 1371 participants, there was a significant difference, d=0.48, in post-treatment fatigue between participants receiving CBT and those in control conditions. Results indicate that CBT for chronic fatigue syndrome tends to be moderately efficacious. Dropout rates in CBT varied from 0-42%, with a mean of 16%. In the five studies that reported the number of CBT clients who were no longer in the clinical range with regard to fatigue at the latest follow-up, the percentage varied from 33% to 73% of those assigned to CBT, with a mean of 50%. Moderator results suggest directions for future investigations.

 

Source: Malouff JM, Thorsteinsson EB, Rooke SE, Bhullar N, Schutte NS. Efficacy of cognitive behavioral therapy for chronic fatigue syndrome: a meta-analysis. Clin Psychol Rev. 2008 Jun;28(5):736-45. Epub 2007 Nov 1. https://www.ncbi.nlm.nih.gov/pubmed/18060672

 

Seven genomic subtypes of chronic fatigue syndrome/myalgic encephalomyelitis: a detailed analysis of gene networks and clinical phenotypes

Abstract:

AIM: Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a multisystem disease, the pathogenesis of which remains undetermined. The authors have recently reported a study of gene expression that identified differential expression of 88 human genes in patients with CFS/ME. Clustering of quantitative PCR (qPCR) data from patients with CFS/ME revealed seven distinct subtypes with distinct differences in Medical Outcomes Survey Short Form-36 scores, clinical phenotypes and severity.

METHODS: In this study, for each CFS/ME subtype, those genes whose expression differed significantly from that of normal blood donors were identified, and then gene interactions, disease associations and molecular and cellular functions of those gene sets were determined. Genomic analysis was then related to clinical data for each CFS/ME subtype.

RESULTS: Genomic analysis revealed some common (neurological, haematological, cancer) and some distinct (metabolic, endocrine, cardiovascular, immunological, inflammatory) disease associations among the subtypes. Subtypes 1, 2 and 7 were the most severe, and subtype 3 was the mildest. Clinical features of each subtype were as follows: subtype 1 (cognitive, musculoskeletal, sleep, anxiety/depression); subtype 2 (musculoskeletal, pain, anxiety/depression); subtype 3 (mild); subtype 4 (cognitive); subtype 5 (musculoskeletal, gastrointestinal); subtype 6 (postexertional); subtype 7 (pain, infectious, musculoskeletal, sleep, neurological, gastrointestinal, neurocognitive, anxiety/depression).

CONCLUSION: It was particularly interesting that in the seven genomically derived subtypes there were distinct clinical syndromes, and that those which were most severe were also those with anxiety/depression, as would be expected in a disease with a biological basis.

 

Source: Kerr JR, Burke B, Petty R, Gough J, Fear D, Mattey DL, Axford JS, Dalgleish AG, Nutt DJ. Seven genomic subtypes of chronic fatigue syndrome/myalgic encephalomyelitis: a detailed analysis of gene networks and clinical phenotypes. J Clin Pathol. 2008 Jun;61(6):730-9. Epub 2007 Dec 5. https://www.ncbi.nlm.nih.gov/pubmed/18057078

 

Successful use of a primary care practice-specialty collaboration in the care of an adolescent with chronic fatigue syndrome

Abstract:

We report on the successful collaborative care of an adolescent with chronic fatigue syndrome between a primary care pediatrician and an academic chronic fatigue syndrome specialist located in different cities. Regular telephone and e-mail communication and clearly defined patient-care roles allowed for timely management of symptoms and marked clinical improvement. We discuss ways to improve the collaboration of primary care and subspecialty physicians for patients with chronic fatigue syndrome and children with special health care needs.

 

Source: Kuo DZ, Cheng TL, Rowe PC. Successful use of a primary care practice-specialty collaboration in the care of an adolescent with chronic fatigue syndrome. Pediatrics. 2007 Dec;120(6):e1536-9. https://www.ncbi.nlm.nih.gov/pubmed/18055669

 

Perception versus polysomnographic assessment of sleep in CFS and non-fatigued control subjects: results from a population-based study

Abstract:

BACKGROUND: Complaints of unrefreshing sleep are a prominent component of chronic fatigue syndrome (CFS); yet, polysomnographic studies have not consistently documented sleep abnormalities in CFS patients. We conducted this study to determine whether alterations in objective sleep characteristics are associated with subjective measures of poor sleep quality in persons with CFS.

METHODS: We examined the relationship between perceived sleep quality and polysomnographic measures of nighttime and daytime sleep in 35 people with CFS and 40 non-fatigued control subjects, identified from the general population of Wichita, Kansas and defined by empiric criteria. Perceived sleep quality and daytime sleepiness were assessed using clinical sleep questionnaires. Objective sleep characteristics were assessed by nocturnal polysomnography and daytime multiple sleep latency testing.

RESULTS: Participants with CFS reported unrefreshing sleep and problems sleeping during the preceding month significantly more often than did non-fatigued controls. Participants with CFS also rated their quality of sleep during the overnight sleep study as significantly worse than did control subjects. Control subjects reported significantly longer sleep onset latency than latency to fall asleep as measured by PSG and MSLT. There were no significant differences in sleep pathology or architecture between subjects with CFS and control subjects.

CONCLUSION: People with CFS reported sleep problems significantly more often than control subjects. Yet, when measured these parameters and sleep architecture did not differ between the two subject groups. A unique finding requiring further study is that control, but not CFS subjects, significantly over reported sleep latency suggesting CFS subjects may have an increased appreciation of sleep behaviour that may contribute to their perception of sleep problems.

 

Source: Majer M, Jones JF, Unger ER, Youngblood LS, Decker MJ, Gurbaxani B, Heim C, Reeves WC. Perception versus polysomnographic assessment of sleep in CFS and non-fatigued control subjects: results from a population-based study. BMC Neurol. 2007 Dec 5;7:40. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2231384/ (Full article)

 

Rehabilitation of decreased motor performance in patients with chronic fatigue syndrome: should we treat low effort capacity or reduced effort tolerance?

Abstract:

AIM: The aetiology, pathophysiology, diagnostic delineation and treatment of chronic fatigue syndrome (CFS) remain a matter of debate. Here some aspects of the debate are elucidated, with a particular focus on the patients’ decreased motor performance.

HYPOTHESIS: The pathophysiological basis of decreased motor performance in CFS may, theoretically, involve three components: (1) a peripheral energetic deficit (impaired oxidative metabolism and/or physical deconditioning); (2) a central perceptual disturbance (higher effort sense or increased ‘interoception’); and (3) a fundamental failure of the neurobiological stress system, leading to an abnormal ‘sickness response’. It is proposed that the first two components may lead to low effort capacity, while the third component may lead to reduced effort tolerance. Although there is evidence for low effort capacity influencing symptoms and functional limitations in CFS, it is assumed that reduced effort tolerance might be the primary disturbance in CFS.

DIAGNOSTIC IMPLICATIONS: Distinguishing low effort capacity and reduced effort tolerance may contribute to a refinement of current diagnostic criteria of CFS and the identification of subgroups.

THERAPEUTIC IMPLICATIONS: The above-mentioned distinction may make it possible to formulate a rationale for an effective implementation and adequate outcome evaluation of rehabilitation strategies in CFS.

RESEARCH IMPLICATIONS: This new heuristic framework may inform future research aimed at disentangling the complex determination of impaired motor performance in CFS, as well as studies aimed at customizing treatment to different subtypes of patients.

 

Source: Van Houdenhove B, Verheyen L, Pardaens K, Luyten P, Van Wambeke P. Rehabilitation of decreased motor performance in patients with chronic fatigue syndrome: should we treat low effort capacity or reduced effort tolerance? Clin Rehabil. 2007 Dec;21(12):1121-42. https://www.ncbi.nlm.nih.gov/pubmed/18042608

 

Immunoassay with cytomegalovirus early antigens from gene products p52 and CM2 (UL44 and UL57) detects active infection in patients with chronic fatigue syndrome

Abstract:

AIMS: To investigate whether the use of recombinant early antigens for detection of antibodies to human cytomegalovirus (HCMV) gene products CM(2) (UL44, UL57) and p52 (UL44) is specific in the diagnosis and differentiation of active HCMV infection in a subset of patients with chronic fatigue syndrome (CFS), a diagnosis which is often missed by the current ELISA assay that uses crude viral lysate antigen.

METHODS: At a single clinic from 1999 to 2001, a total of 4774 serological tests were performed in 1135 patients with patients using two immunoassays, Copalis and ELISA. The Copalis immunoassay utilised HCMV early gene products of UL44 and UL57 recombinant antigens for detection of HCMV IgM antibody, and viral capsid antigen for detection of HCMV IgG antibody. The ELISA immunoassay utilised viral crude lysate as antigen for detection of both HCMV IgG and IgM.

RESULTS: 517 patients (45.6%) were positive for HCMV IgG by both assays. Of these, 12 (2.2%) were positive for HCMV(V) IgM serum antibody by HCMV ELISA assay, and 61 (11.8%) were positive for IgM HCMV serum antibody by Copalis assay. The Copalis assay that uses HCMV early recombinant gene products CM(2) (UL44, UL57) and p52 (UL44) in comparison with ELISA was 98% specific.

CONCLUSIONS: Immunoassays that use early antigen recombinant HCMV CM(2) and p52 are five times more sensitive than HCMV ELISA assay using viral lysate, and are specific in the detection and differentiation of active HCMV infection in a subset of patients with CFS.

 

Source: Beqaj SH, Lerner AM, Fitzgerald JT. Immunoassay with cytomegalovirus early antigens from gene products p52 and CM2 (UL44 and UL57) detects active infection in patients with chronic fatigue syndrome. J Clin Pathol. 2008 May;61(5):623-6. Epub 2007 Nov 23. https://www.ncbi.nlm.nih.gov/pubmed/18037660

 

Actigraphic assessment of sleep disorders in children with chronic fatigue syndrome

Abstract:

Children with chronic fatigue syndrome (CFS) often suffer from sleep disorders, which cause many physiological and psychological problems. Understanding sleep characteristics in children with CFS is important for establishing a therapeutic strategy. We conducted an actigraphic study to clarify the problems in sleep/wake rhythm and physical activity in children with CFS.

METHODS: Actigraphic recordings were performed for 1-2 weeks in 12 CFS children. The obtained data were compared with those of healthy age-matched children used as the control.

RESULTS: Sleep patterns were divided into two groups based on subjects’ sleep logs: irregular sleep type and delayed sleep phase type. Compared to the control group, total sleep time was longer and physical activity was lower in both groups of CFS. Continuous sleep for more than 10h was not uncommon in CFS. In the irregular sleep type, impaired daily sleep/wake rhythms and disrupted sleep were observed.

CONCLUSION: Using actigraphy, we could identify several characteristics of the sleep patterns in CFS children. Actigraphic analysis proved to be useful in detecting sleep/wake problems in children with CFS.

 

Source: Ohinata J, Suzuki N, Araki A, Takahashi S, Fujieda K, Tanaka H. Actigraphic assessment of sleep disorders in children with chronic fatigue syndrome. Brain Dev. 2008 May;30(5):329-33. Epub 2007 Nov 26. https://www.ncbi.nlm.nih.gov/pubmed/18031961