Chronic Fatigue Syndrome: O'Neill W

Lerner AM, Beqaj SH, Deeter RG, Dworkin HJ, Zervos M, Chang CH, Fitzgerald JT, Goldstein J, O'Neill W. · School of Medicine, Wayne State University, Detroit, MI, USA. · Drugs Today (Barc). · Pubmed #12582420 No free full text.

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.

Lerner AM, Zervos M, Chang CH, Beqaj S, Goldstein J, O'Neill W, Dworkin H, Fitgerald T, Deeter RG. · No affiliation provided · Clin Infect Dis. · Pubmed #11340544 No free full text.

This publication has no abstract.

Lerner AM, Dworkin HJ, Sayyed T, Chang CH, Fitzgerald JT, Beqaj S, Deeter RG, Goldstein J, Gottipolu P, O'Neill W. · Department of Medicine, William Beaumont Hospital, Royal Oak, Michigan, USA. · In Vivo. · Pubmed #15369178 No free full text.

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.