subgroups – Page 5 – American ME and CFS Society

Mycoplasma blood infection in chronic fatigue and fibromyalgia syndromes

Abstract:

Chronic fatigue syndrome (CFS) and fibromyalgia syndrome (FMS) are characterised by a lack of consistent laboratory and clinical abnormalities. Although they are distinguishable as separate syndromes based on established criteria, a great number of patients are diagnosed with both.

In studies using polymerase chain reaction methods, mycoplasma blood infection has been detected in about 50% of patients with CFS and/or FMS, including patients with Gulf War illnesses and symptoms that overlap with one or both syndromes. Such infection is detected in only about 10% of healthy individuals, significantly less than in patients.

Most patients with CFS/FMS who have mycoplasma infection appear to recover and reach their pre-illness state after long-term antibiotic therapy with doxycycline, and the infection can not be detected after recovery. By means of causation and therapy, mycoplasma blood infection may permit a further subclassification of CFS and FMS.

It is not clear whether mycoplasmas are associated with CFS/FMS as causal agents, cofactors, or opportunistic infections in patients with immune disturbances. Whether mycoplasma infection can be detected in about 50% of all patient populations with CFS and/or FMS is yet to be determined.

Source: Endresen GK. Mycoplasma blood infection in chronic fatigue and fibromyalgia syndromes. Rheumatol Int. 2003 Sep;23(5):211-5. Epub 2003 Jul 16. http://www.ncbi.nlm.nih.gov/pubmed/12879275

Autoantibodies against muscarinic cholinergic receptor in chronic fatigue syndrome

Abstract:

The disturbance of the central nervous system and immunological abnormalities have been suggested in patients with chronic fatigue syndrome(CFS). We focused on immunological abnormalities against neurotransmitter receptors in CFS.

Using a sensitive radioligand assay, we examined serum autoantibodies to recombinant human muscarinic cholinergic receptor 1 (CHRM1), mu-opioid receptor (OPRM1), 5-hydroxytryptamine receptor 1A (HTR1A), and dopamine receptor D2 (DRD2) in patients with CFS (n=60) and results were compared with those in patients with autoimmune disease (n=33) and in healthy controls (n=30).

The mean anti-CHRM1 antibody index was significantly higher in patients with CFS (p<0.0001) and autoimmune disease (p<0.05) than that in healthy controls, and positive reaction was found in 53.3% of patients with CFS. Anti-OPRM1 antibodies, anti-HTR1A antibodies, and anti-DRD2 antibodies were found in 15.2, 1.7, and 5.0% of patients with CFS, respectively. Anti-nuclear antibodies were found in 56.7% (34/60) of patients with CFS, but anti-nuclear antibody titers did not correlate with the activities of the above four autoantibodies.

The patients with positive autoantibodies to CHRM1 had a significantly higher mean score (1.81) of ‘feeling of muscle weakness’ than negative patients (1.18) among CFS patients (p<0.01). Higher scores on ‘painful node’, ‘forgetfulness’, and ‘difficulty thinking’ were also found in CFS patients with anti-CHRM1 antibodies but did not reach statistical significance.

In conclusion, autoantibodies to CHRM1 were detected in a large number of CFS patients and were related to CFS symptoms. Our findings suggested that subgroups of CFS are associated with autoimmune abnormalities of CHRM1.

Source: Tanaka S, Kuratsune H, Hidaka Y, Hakariya Y, Tatsumi KI, Takano T, Kanakura Y, Amino N. Autoantibodies against muscarinic cholinergic receptor in chronic fatigue syndrome. Int J Mol Med. 2003 Aug;12(2):225-30. http://www.ncbi.nlm.nih.gov/pubmed/12851722

Observer independent analysis of cerebral glucose metabolism in patients with chronic fatigue syndrome

Abstract:

OBJECTIVES: To evaluate cerebral glucose metabolism, assessed by 18-fluorodeoxyglucose positron emission tomography (FDG-PET), in patients with chronic fatigue syndrome (CFS), using an observer independent analytical approach; and to characterise any observed alterations by correlating them with neuropsychological deficits.

METHODS: 26 patients (13 female, 13 male) were examined. They all fulfilled the CDC diagnostic criteria for CFS. Their ages ranged from 26 to 61 years (mean (SD) age, 43 (9.3) years). They underwent extensive psychometric testing including the hospital anxiety and depression scale (HADS) and the short form 36 item health questionnaire (SF-36). Brain FDG-PET was done in all the subjects. After stereotactic normalisation, single subject comparisons with an age and sex matched normal database (n = 18) and a group comparison between the patients and normal controls were undertaken, along with additional correlation analyses between brain metabolism and psychometric test scores.

RESULTS: 12 of the 26 patients showed no significant decrease in FDG uptake compared with the controls. Of the remaining 14, 12 showed hypometabolism bilaterally in the cingulate gyrus and the adjacent mesial cortical areas. Five of these 12 patients also had decreased metabolism in the orbitofrontal cortex. The two remaining patients had hypometabolism in the cuneus/praecuneus. Correlation analyses showed significant correlations between some test scores (anxiety, depression, health related quality of life) but not fatigue and regional reductions in glucose metabolism.

CONCLUSIONS: Although abnormalities in FDG-PET were only detectable in approximately half the CFS patients examined, and no specific pattern for CFS could be identified, PET may provide valuable information in helping to separate CFS patients into subpopulations with and without apparent alterations in the central nervous system.

Source: Siessmeier T, Nix WA, Hardt J, Schreckenberger M, Egle UT, Bartenstein P. Observer independent analysis of cerebral glucose metabolism in patients with chronic fatigue syndrome. J Neurol Neurosurg Psychiatry. 2003 Jul;74(7):922-8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1738575/ (Full article)

Subclassifying chronic fatigue syndrome through exercise testing

Abstract:

PURPOSE: The purpose of this study was to examine physiological responses of persons with chronic fatigue syndrome (CFS) to a graded exercise test.

METHODS: Cardiopulmonary exercise tests were performed on 189 patients diagnosed with CFS. Based on values for peak oxygen consumption, patients were assigned to one of four impairment categories (none, mild, moderate, and severe), using American Medical Association (AMA) guidelines. A one-way MANOVA was used to determine differences between impairment categories for the dependent variables of age, body mass index, percentage of predicted [OV0312]O(2), resting and peak heart rates, resting and peak systolic blood pressure, respiratory quotient (RQ), and rating of perceived exertion.

RESULTS: Significant differences were found between each impairment level for percentage of predicted [OV0312]O(2) and peak heart rate. Peak systolic blood pressure values for the “moderate,” and “severe” groups differed significantly from each other and both other groups. The more impaired groups had lower values. The no impairment group had a significantly higher peak RQ than each of the other impairment levels (all P < 0.001). Peak [OV0312]O(2) values were less than predicted for all groups. Compared with the males, the women achieved actual values for peak [OV0312]O(2) that were closer to their predicted values.

CONCLUSION: Despite a common diagnosis, the functional capacity of CFS patients varies greatly. Stratifying patients by function allows for a more meaningful interpretation of the responses to exercise and may enable differential diagnosis between subsets of CFS patients.

Comment in: Physiological factors limiting exercise performance in CFS. [Med Sci Sports Exerc. 2004]

Source: Vanness JM, Snell CR, Strayer DR, Dempsey L 4th, Stevens SR. Subclassifying chronic fatigue syndrome through exercise testing. Med Sci Sports Exerc. 2003 Jun;35(6):908-13. http://www.ncbi.nlm.nih.gov/pubmed/12783037

Predictive immunophenotypes: disease-related profile in chronic fatigue syndrome

Abstract:

BACKGROUND: There is a growing body of evidence supporting the theory that problems with immune function play an important role in chronic fatigue syndrome (CFS).

METHODS: We studied 90 CFS cases and 50 healthy controls from two different areas of upstate New York to determine whether there were differences in the absolute number and pattern of natural killer (NK) and cytotoxic T-cell phenotypes between CFS cases and healthy controls in the two regions. One group was from a small town where a cluster of cases existed; the other was from a large metropolitan area where there was not a known cluster.

RESULTS: The number of CD56+CD3+CD8+ and CD56+CD3+CD8- cells in cases from the two areas were both significantly elevated over that of controls from the metropolitan area (P < 0.03). The number of CD56+CD3-CD8+ and CD56+CD3-CD8- cells was significantly reduced in the two case groups compared to that of controls from the metropolitan area (P = 0.04). However, controls who were from the same town as the cluster cases had numbers of CD56+CD3+CD8+, CD56+CD3+CD8-, and CD56+CD3-CD8- cells that were more like that of cases than controls. Only the number of CD56+CD3-CD8+ cells (an NK cell subset) was significantly different in cases versus controls from the cluster area (P = 0.022).

CONCLUSIONS: These data suggest that differences in controls from cluster and noncluster areas may be responsible for some of the inconsistencies in results from other studies. Furthermore, they suggest the possibility that NK cell function may play an important role in preventing the development of CFS in individuals who live in a community where a cluster of cases have been identified.

Source: Stewart CC, Cookfair DL, Hovey KM, Wende KE, Bell DS, Warner CL. Predictive immunophenotypes: disease-related profile in chronic fatigue syndrome. Cytometry B Clin Cytom. 2003 May;53(1):26-33. http://onlinelibrary.wiley.com/doi/10.1002/cyto.b.10034/full (Full article)

Variability in diagnostic criteria for chronic fatigue syndrome may result in substantial differences in patterns of symptoms and disability

Abstract:

Chronic fatigue syndrome (CFS) is an illness that involves severe, prolonged exhaustion as well as neurologic, immunologic, and endocrine system pathology. Because the pathogenesis of CFS has yet to be determined, case definitions have relied on clinical observation in classifying signs and symptoms for diagnosis.

The current investigation examined differences between CFS as defined by Fukuda and colleagues and a set of criteria that has been stipulated for myalgic encephalomyelitis (ME). Dependent measures included psychiatric comorbidity, symptom frequency, symptom severity, and functional impairment. The ME and Fukuda et al. (1994) CFS criteria were compared with a group having chronic fatigue due to psychiatric reasons.

Significant differences occurred primarily with neurologic, neuropsychiatric, fatigue/weakness, and rheumatological symptoms. These findings suggest that it might be inappropriate to synthesize results from studies of this illness that use different definitions to select study populations.

Source: Jason LA, Helgerson J, Torres-Harding SR, Carrico AW, Taylor RR. Variability in diagnostic criteria for chronic fatigue syndrome may result in substantial differences in patterns of symptoms and disability. Eval Health Prof. 2003 Mar;26(1):3-22. http://www.ncbi.nlm.nih.gov/pubmed/12629919

Chronic fatigue syndrome: symptom subtypes in a community based sample

Abstract:

Most studies of Chronic Fatigue Syndrome (CFS) have been based on patients recruited from primary or tertiary care settings. Patients from such settings might not be typical of patients in the general population. The present investigation involved examining individuals with CFS from a community-based study. A random sample of 18,675 respondents in Chicago were first interviewed by telephone. A group of individuals with chronic fatigue accompanied by at least four Fukuda et al. (1994) symptoms associated with CFS were given medical and psychiatric examinations. From this sample, a physician review group diagnosed individuals with CFS. Those diagnosed with CFS were subclassified based on frequency of symptoms. Important differences emerged on measures of sociodemographics and disability. The implications of these findings and others are discussed.

Source: Jason LA, Taylor RR, Kennedy CL, Jordan KM, Song S, Johnson D, Torres-Harding S. Chronic fatigue syndrome: symptom subtypes in a community based sample. Women Health. 2003;37(1):1-13. http://www.ncbi.nlm.nih.gov/pubmed/12627607

A six-month trial of valacyclovir in the Epstein-Barr virus subset of chronic fatigue syndrome: improvement in left ventricular function

Abstract:

This study was designed to determine safety and efficacy of a 6-month trial of valacyclovir in single-virus Epstein-Barr virus (EBV) persistent infection. Phase I of this study used four specific criteria to define a subset of patients with chronic fatigue syndrome (CFS). In the second phase, myocardial dynamics were measured by MUGA rest/stress radionuclide ventriculographic (RVG) examinations pre- and posttreatment with valacyclovir.

In phase I, a trial was performed in 19 consecutive CFS patients with the following diagnostic conditions: patients met criteria for diagnosis of CFS; they had had CFS for less than 1 year. They demonstrated repetitively abnormal oscillating T waves (ischemic or flat) at 24-h Holter monitoring; and they had elevated serum IgM antibody titers to EBV viral capsid antigen and/or total diffuse early antigen as measured by the enzyme-linked immunosorbent assay method.

The treatment group comprised 10 CFS patients with no serum antibodies to human cytomegalovirus, but the control group (nine CFS patients) had, additionally, high titers of serum antibodies (IgG) to conformational structural antigens of human cytomegalovirus. Both the parallel treatment and control CFS groups received valacyclovir 1.0-1.5 gm q.6.h. for 6 months.

This valacyclovir dose achieved serum acyclovir C(max) of > 7 microm and high antiviral activity versus EBV (IC(50) of 4.4-13.3 m). In phase II, six additional CFS patients met the same four criteria as the 19 CFS patients in phase I. They had, however, been ill for a mean of 55.8 months. Thus, 25 CFS patients comprise this study.

The studies were carried out at a single outpatient practice in Birmingham, MI, U.S.A. Before initiating valacyclovir, and after 6 months of treatment, clinical and laboratory observations were made. The CFS Energy Index point score (Table I) was used to record each CFS patient’s functional capacity at baseline and after 1, 3 and 6 months of valacyclovir. Energy Index point scores, as well as EBV and human cytomegalovirus serum antibody titers were assessed.

In the second phase, left ventricular dynamics were repeated after 6 months of treatment with valacyclovir. We concluded that the 16 CFS patients (included in both phases of this study) with EBV-persistent infection (EBV single-virus subset) are improved after 6 months of continuous pharmacokinetic dosing with valacyclovir. Nine CFS patients with EBV/human cytomegalovirus co-infection did not benefit from 6 months of similar treatment. Valacyclovir is not an effective anti-human cytomegalovirus antiviral drug. Unimproved CFS patients with co-infections EBV and human cytomegalovirus may require combined treatment with valacyclovir and another drug more active against human cytomegalovirus.

This preliminary trial, with a small number of patients, may be critical to an appropriately designed larger, double-blind, placebo-controlled trial.

Source: Lerner AM, Beqaj SH, Deeter RG, Dworkin HJ, Zervos M, Chang CH, Fitzgerald JT, Goldstein J, O’Neill W. A six-month trial of valacyclovir in the Epstein-Barr virus subset of chronic fatigue syndrome: improvement in left ventricular function. Drugs Today (Barc). 2002 Aug;38(8):549-61. http://www.ncbi.nlm.nih.gov/pubmed/12582420

A status report on chronic fatigue syndrome

Abstract:

Medical history has shown that clinical disease entities or syndromes are composed of many subgroups–each with its own cause and pathogenesis. Although we cannot be sure, we expect the same outcome for chronic fatigue syndrome (CFS), a medically unexplained condition characterized by disabling fatigue accompanied by infectious, rheumatological, and neuropsychiatric symptoms. Although the ailment clearly can occur after severe infection, no convincing data exist to support an infectious (or immunologic) process in disease maintenance. Instead, data point to several possible pathophysiological processes: a covert encephalopathy, impaired physiological capability to respond to physical and mental stressors, and psychological factors related to concerns about effort exacerbating symptoms. Each of these is under intense investigation. In addition, some data do exist to indicate that environmental agents also can elicit a state of chronic fatigue. We expect data to accumulate to support the belief that CFS has multiple causes.

Source: Natelson BH, Lange G. A status report on chronic fatigue syndrome. Environ Health Perspect. 2002 Aug;110 Suppl 4:673-7. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1241224/ (Full article)

IgM serum antibodies to human cytomegalovirus nonstructural gene products p52 and CM2(UL44 and UL57) are uniquely present in a subset of patients with chronic fatigue syndrome

Abstract:

Human cytomegalovirus (HCMV) IgM serum antibodies to two nonstructural gene products UL44 and UL57 (p52 and CM2) were assayed in patients with the diagnosis of the chronic fatigue syndrome (CFS) according to criteria established by the US Centers for Disease Control and Prevention. A subset of 16 CFS patients demonstrated HCMV IgG, but no HCMV IgM serum antibodies to conformational structural HCMV antigens (designated, V). By convention, these findings are interpreted to indicate only a remote HCMV infection.

However, HCMV IgM p52 and CM2 antibodies were uniquely present in these 16 CFS patients. Other CFS patients with similar HCMV (V) IgG antibodies (18 patients), non-fatigued HCMV (V) IgG-positive control patients (18 patients), random HCMV (V) IgG-positive control patients from a clinical laboratory (26 patients), and non-fatigued HCMV (V) IgG-negative control patients (15 patients) did not have HCMV, IgM p52 or CM2 serum antibodies (p < 0.05). Control HCMV (V) IgG-positive patients had no serum IgM HCMV (V) antibodies to conventional structural HCMV (V) antigen. Thus, 77 various control patients did not contain IgM p52 or CM2 serum antibodies. The presence of IgM p52 and/or CM2 HCMV serum antibodies in this subset of CSF-specific patients may detect incomplete HCMV multiplication in which a part of the HCMV protein-coding content of the HCMV genome is processed, but remains unassembled.

These findings suggest that the presence of HCMV IgM p52 and CM2 serum antibodies may be a specific diagnostic test for the diagnosis of a subset of CFS patients. Further, these data suggest an etiologic relationship for HCMV infection in this group of CFS patients

Source: Lerner AM, Beqaj SH, Deeter RG, Fitzgerald JT. IgM serum antibodies to human cytomegalovirus nonstructural gene products p52 and CM2(UL44 and UL57) are uniquely present in a subset of patients with chronic fatigue syndrome. In Vivo. 2002 May-Jun;16(3):153-9. http://www.ncbi.nlm.nih.gov/pubmed/12182109