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Query: UMLS:C0015674 (chronic fatigue syndrome)
 2,978 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Despite its new name, chronic fatigue syndrome is not a new disease. This chapter reviews current definitions, emphasizing that chronic fatigue syndrome is a diagnosis of exclusion. The author also discusses viral infections that are associated with CFS, including Epstein-Barr virus, cytomegalovirus, herpesvirus type 6, enteroviruses, and retroviruses.
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PMID:Chronic Fatigue Syndrome. 1035 5

Herpesviruses, in particular Epstein-Barr virus (EBV), cytomegalovirus (CMV) and human herpesvirus 6 (HHV-6), have, for the past two decades, come under considerable scrutiny as aetiological agents of chronic fatigue syndrome (CFS). However, virological findings of herpesviruses in CFS have not been consistent between different studies, and the unusual patterns of serological responses to EBV, CMV and HHV-6 have not been specific for CFS, being observed also in asymptomatic individuals. In addition, patients with symptomatology suggestive of CFS do not appear to have an increased frequency of these herpesviruses, as detected by culture or polymerase chain reaction, compared with controls, which argues against an ongoing active herpetic infection. Studies have also shown that the presumable elevation of antibody titres to EBV, CMV or HHV-6 in CFS are not observed only with these viruses, but also with other organisms such as herpes simplex virus and measles.
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PMID:Chronic Fatigue Syndrome and Herpesviruses: the Fading Evidence. 1186 1

To estimate the prevalence of viruses associated with chronic fatigue syndrome (CFS) and to control for genetic and environmental factors, we conducted a co-twin control study of 22 monozygotic twin pairs, of which one twin met criteria for CFS and the other twin was healthy. Levels of antibodies to human herpesvirus (HHV)-8, cytomegalovirus, herpes simplex virus 1 and 2, and hepatitis C virus were measured. Polymerase chain reaction (PCR) assays for viral DNA were performed on peripheral blood mononuclear cell specimens to detect infection with HHV-6, HHV-7, HHV-8, cytomegalovirus, Epstein-Barr virus, herpes simplex virus, varicella zoster virus, JC virus, BK virus, and parvovirus B19. To detect lytic infection, plasma was tested by PCR for HHV-6, HHV-8, cytomegalovirus, and Epstein-Barr virus DNA, and saliva was examined for HHV-8 DNA. For all assays, results did not differ between the group of twins with CFS and the healthy twins.
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PMID:Markers of viral infection in monozygotic twins discordant for chronic fatigue syndrome. 1259 50

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.
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PMID: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. 1218 9

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.
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PMID:A six-month trial of valacyclovir in the Epstein-Barr virus subset of chronic fatigue syndrome: improvement in left ventricular function. 1258 20

We examined 100 symptomatic Gulf War veterans (patients) and 100 controls for immunologic assays. The veterans and controls were compared for the percentage of T cells (CD3); B cells (CD19); helper:suppressor (CD4:CD8) ratio; natural killer (NK) cell activity; mitogenic response to phytohemagglutin (PHA) and pokeweed mitogen (PWM); level of immune complexes; myelin basic protein (MBP) and striated and smooth muscle autoantibodies; and antibodies against Epstein-Barr virus, cytomegalovirus, herpes simplex virus type 1 (HSV-1), HSV-2, human herpes Type 6 (HHV-6), and Varicella zoster virus (VZV). The percentage of T cells in patients versus controls was not significantly different, whereas a significantly higher proportion of patients had elevated T cells compared with controls. The percentage of B cells was significantly elevated in the patients versus the controls. The NK cell (NK) activity was significantly decreased in the patients (24.8 +/- 16.5 lytic units) versus the controls (37.3 +/- 26.4 lytic units). The percentage of patients with lower than normal response to PHA and PWM was significantly different from controls. Immune complexes were significantly increased in the patients (53.1 +/- 18.6, mean +/- SD) versus controls (34.6 +/- 14.3). Autoantibody titers directed against MBP and striated or smooth muscle were significantly greater in patients versus controls. Finally, the patients had significantly greater titers of antibodies to the viruses compared with the controls (p < 0.001). These immune alterations were detected 2-8 years after participation in the Gulf War. The immune alterations are consistent with exposure to different environmental factors. We conclude that Gulf War syndrome is a multifaceted illness with immune function alterations that may be induced by various factors and are probably associated with chronic fatigue syndrome.
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PMID:Cellular and humoral immune abnormalities in Gulf War veterans. 1517 70

We reported unique incomplete herpesvirus (Epstein-Barr Virus (EBV) and/or nonstructural (HCMV) cytomegalovirus) multiplication in 2 distinct subsets of CFS patients. The CFS subsets were identified by: a) presence of IgM serum antibodies to HCMV nonstructural gene products p52 and CM2 (UL44 and UL57), and/or b) IgM serum antibodies to Epstein-Barr virus viral capsid antigen (EBV, VCA IgM). Diagnostic IgM serum antibodies were found in two independent blinded studies involving 49 CFS patients, but the same antibodies were absent in 170 control patients (p<0.05). Abnormal 24 Hr-electrocardiographic monitoring, tachycardias at rest and, in severe chronic cases, abnormal cardiac wall motion (ACWM) were seen in these same CFS patients. We now report a prospective consecutive case control study from 1987--1999 of cardiac dynamics as measured by radionuclide ventriculography in 98 CFS patients from 1987--1999. Controls were patients with various malignancies who were evaluated in protocols requiring radionuclide ventriculography before initiation of cardiotoxic chemotherapeutic agents. The prevalence of abnormal cardiac wall motion (ACWM) at rest in CFS patients was 10 out of 87 patients (11.5%). With stress exercise, 21 patients (24.1%) demonstrated ACWM. Cardiac biopsies in 3 of these CFS patients with ACWM showed a cardiomyopathy. Among the controls, ACWM at rest was present in 4 out of 191 patients (2%) (p=0.0018). A progressive cardiomyopathy caused by incomplete virus multiplication of EBV and/or HCMV in CFS patients is present.
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PMID:Prevalence of abnormal cardiac wall motion in the cardiomyopathy associated with incomplete multiplication of Epstein-barr Virus and/or cytomegalovirus in patients with chronic fatigue syndrome. 1536 78

This article posits that infection of the peripheral ganglia causes at least some cases of Chronic Fatigue Syndrome (CFS), with a neurotropic herpesvirus, particularly varicella-zoster virus (VZV), as the most likely cause of the infection. Virtually all CFS symptoms could be produced by an infection of the peripheral ganglia, with infection of the autonomic ganglia causing fatigue, postural hypotension, and sleep disturbances, and infection of the sensory ganglia causing sensory symptoms such as chronic pain. Furthermore, infections of the peripheral ganglia are known to cause long-term nerve dysfunction, which would help explain the chronic course of CFS. Herpesviruses have long been suspected as the cause of CFS; this theory has recently been supported by studies showing that administering antiherpes agents causes substantial improvement in some CFS patients. VZV is known to frequently reactivate in the peripheral ganglia of previously healthy adults and cause sudden, debilitating illness, making it a likely candidate as a cause of CFS. Moreover, many of the symptoms of CFS overlap with those of herpes zoster (shingles), with the exception that painful rash is not one of the symptoms of CFS. A model is therefore proposed in which CFS is one of the many manifestations of zoster sine herpete; that is, herpes zoster without rash. Furthermore, re-exposure to VZV in the form of chickenpox has become less common in the past few decades; without such re-exposure, immunity to VZV drops, which could explain the increased incidence of CFS. Co-infection with multiple herpesviruses is a possibility, as some CFS patients show signs of infection with other herpesviruses including Epstein-Barr, Cytomegalovirus, and HHV6. These three herpesviruses can attack immune cells, and may therefore promote neurotropic herpesvirus reactivation in the ganglia. The possibility of VZV as the causal agent in CFS has previously received almost no attention; the possibility that CFS involves infection of the peripheral ganglia has likewise been largely overlooked. This suggests that the search for a viral cause of CFS has been far from exhaustive. Several antiherpes drugs are available, as is a vaccine for VZV; more research into such agents as possible treatments for CFS is urgently needed.
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PMID:Does varicella-zoster virus infection of the peripheral ganglia cause Chronic Fatigue Syndrome? 1952 May 22

Multiple previous studies have sought evidence for ongoing, active infection with, or reactivation of, Herpesviruses in patients with chronic fatigue syndrome (CFS), with conflicting results. This study aimed to clarify this by studying 20 patients enrolled in a well-characterized model of the onset and evolution of CFS, the prospective cohort of the Dubbo Infection Outcomes Study (DIOS). The patients selected for examination included five CFS patients with primary Epstein-Barr virus (EBV) infection; five CFS patients with acute viral infection not caused by EBV; and 10 matched controls with prompt resolution of primary EBV infection. Serum samples from three timepoints were assayed using a comprehensive range of serological assays for EBV, HHV-6, and CMV. Viral genomes were assessed using quantitative PCR assays. All patients were seropositive for HHV-6, and 10 were seropositive for CMV at infection baseline (five patients and five controls). Low titer CMV IgM antibodies were found at infection baseline in two of these cases and three control patients. HHV-6 IgG antibody titers were highest at infection baseline but did not differ between the CFS cases and the control patients. There were increases in EBV IgG VCA p18, EBNA-1 IgG, and EA IgG titers over time, but these did not differ between CFS cases and control patients. EBV and HHV6 DNA levels were at control levels in a minority of samples, and CMV was undetectable in all samples. These data do not support the hypothesis of ongoing or reactivated EBV, HHV-6, or CMV infection in the pathogenesis of CFS.
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PMID:Serological and virological investigation of the role of the herpesviruses EBV, CMV and HHV-6 in post-infective fatigue syndrome. 2082 65

The cause of chronic fatigue syndrome (CFS) is still enigmatic. Using indirect immunofluorescence testing for measuring antibody against human herpesvirus 6 (HHV-6), this study investigated the association of CFS with infection by HHV-6. Seventeen patients (group A) fulfilling the Centers for Disease Control (CDC) definition for CFS were compared with eight patients (group B) with chronic fatigue but not meeting the CDC criteria. No significant difference was found between the two groups for 30 parameters including sex, age, exposure to children and serology for Epstein-Barr virus, cytomegalovirus, herpes simplex virus, and toxoplasma. Univariate analysis showed that patients in group A complained more frequently of a sore throat, headache and of recurrent type of fatigue. These three parameters are discriminant in identifying patients who will meet the CDC case definition of CFS. The titre of antibody against HHV-6 in group A (1:99) was significantly higher than in group B (1:15) (P=0.007). Elevated HHV-6 titres suggests that this virus could be a cofactor in the pathogenesis of CFS.
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PMID:Human herpesvirus 6 and chronic fatigue syndrome. 2234 48


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