Tag: Goldstein

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

Abstract:

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.

 

Source: Lerner AM, Dworkin HJ, Sayyed T, Chang CH, Fitzgerald JT, Beqaj S, Deeter RG, Goldstein J, Gottipolu P, O’Neill W. 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. In Vivo. 2004 Jul-Aug;18(4):417-24. http://iv.iiarjournals.org/content/18/4/417.long (Full article)

 

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.

Copyright 2002 Prous Science

 

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 small, randomized, placebo-controlled trial of the use of antiviral therapy for patients with chronic fatigue syndrome

Comment on: Editorial response: microbial persistence and idiopathic dilated cardiomyopathy. [Clin Infect Dis. 1999]

 

SIR—We have presented controlled and observational data that are consistent with the hypothesis that subsets of cases of chronic fatigue syndrome (CFS) result from cardiac disease due to a single, persisting infection caused by Epstein-Barr virus (EBV) or, in turn, to a single, persisting infection caused by human cytomegalovirus (HCMV) in immunocompetent patients [1]. Patients who have a separate subset of CFS have simultaneous coinfection with EBV and HCMV. Cardiomyopathic changes are observed in right ventricular endomyocardial biopsy specimens obtained from such patients, and abnormal findings on Holter monitoring (e.g., oscillating abnormal T-wave flattenings and T-wave inversions) are “uniformly” present [2–4]. Left ventricular dysfunction is manifested by sinus tachycardia at rest, abnormal cardiac-wall motion, and decreased left ventricular ejection fractions (rest/stress) in those patients with CFS who are most ill [5]. These findings belie the relatively normal findings observed on standard 12-lead electrocardiograms [6].

In January 1995, a double-blinded, placebo-controlled, phase III crossover study of patients with CFS was initiated. Eleven patients who had CFS (10 of whom were women) were each followed for 18 consecutive months. The mean patient age was 42.7 years, and the mean duration of CFS was 35.1 months. Before antiviral nucleosides were administered, endomyocardial biopsies were performed. Cardiac tissues and blood samples tested negative for isolation of HCMV in cultures of human fibroblast tissues. Two cardiac biopsy specimens that were obtained from patients who had CFS tested positive for HCMV nucleic acids by means of PCR. No cardiac specimen that was obtained from a patient with CFS tested positive for EBV nucleic acids. (Cardiac tissue samples that were obtained from 4 of 21 control patients who had coronary artery disease but who did not have CFS also tested positive for HCMV nucleic acids.) Cardiomyopathic degenerative findings (e.g., myofiber disarray, interstitial fibrosis, increased intracellular granules, and interstitial fat) were noted in patients who had CFS. One patient who had CFS had myocarditis with focal lymphocytic infiltrates.

You can read the rest of this article here: http://cid.oxfordjournals.org/content/32/11/1657.long

 

Source: Lerner AM, Zervos M, Chang CH, Beqaj S, Goldstein J, O’Neill W, Dworkin H, Fitgerald T, Deeter RG. A small, randomized, placebo-controlled trial of the use of antiviral therapy for patients with chronic fatigue syndrome. Clin Infect Dis. 2001 Jun 1;32(11):1657-8. http://cid.oxfordjournals.org/content/32/11/1657.long (Full article)

 

Memory deficits associated with chronic fatigue immune dysfunction syndrome

Abstract:

Performance on tests of memory in 39 patients who met Center for Disease Control (CDC) criteria for chronic fatigue immune dysfunction syndrome (CFIDS) was compared with 23 depressed patients (DSM-III-R) and 129 healthy controls.

Although the CFIDS patients had normal neuropsychological profiles, they significantly overestimated their ability (metamemory), performed significantly worse on tests of recall as context increased (e.g., recognition), made more errors when rehearsal was prevented, and had delayed mental scanning as memory load increased.

The overall pattern indicated that CFIDS patients had a significant memory deficit, far worse than implied by CDC criteria. The pattern for CFIDS patients was consistent with temporal-limbic dysfunction and significantly different than depressed patients and control subjects.

 

Source: Sandman CA, Barron JL, Nackoul K, Goldstein J, Fidler F. Memory deficits associated with chronic fatigue immune dysfunction syndrome. Biol Psychiatry. 1993 Apr 15-May 1;33(8-9):618-23. http://www.ncbi.nlm.nih.gov/pubmed/8329493