A. Martin Lerner, Marcus Zervos, Howard J. Dworkin, Chug-ho Chang, James T. Fitzgerald, James Goldstein, Claudine Lawrie-Hoppen, Barry Franklin, Steven M. Korotkin, Marc Brodsky, Daniel Walsh, and William O'Neil.

Infectious Disease in Clinical Practice, 1997;6:110-117

Authors' summary: We describe a subset of patients with chronic fatigue syndrome (CFS/ME) as defined by the CDC, a duration of overwhelming fatigue for <2 years, and oscillating repetitively abnormal aberrant T-waves at 24-hour electrocardiogram (ECG) recordings (Holter monitors). Baseline 12-lead ECF, 2-D echocardiogram, rest/stress myocardial perfusion (thallium 201 or TC-99 sestamibi) and rest/stress multiple-gated acquisition studies, as well as coronary angiography excluded coronary artery disease. Patients in this CFS/ME subset had significant Ig (with or without positive IgM) human cytomegalovirus enzyme-linked immunoassay antibody titers. They had little or no evidence of concurrent Epstein-Barr virus (EBV) multiplication, corroborated by negative viral capsid antigen IgM antibody titer and an EBV total early antigen antibody of 40. Patients were given intravenous ganciclovir (5 mg/kg 1 12 h for 30 days). Before this treatment, none of 18 patients could work or manage a household. At evaluations, 24 weeks after ganciclovir, 13 patients (72%) returned to their premorbid health states (P<.05). There were no adverse effects from ganciclovir in these nonimmunosuppressed patients.

Introduction: CFS/ME is a disorder the natural history, clinical characteristics, pathologic physiology, and treatment of which remain uncertain... [etc. etc]

Since the fatigue of the mononucleosis syndrome resembles that of the CFS/ME, we assayed antibodies to human cytomegalovirus (HCMV) and Epstein-Barr virus. High antibody titers to toxoplasmosis, an occasional cause of the mononucleosis syndrome, are unusual in CFS/ME patients.

[Quotes and summarizes Rowe and colleagues NMH studies, then state:] The authors concluded that neurally mediated hypotension is a cause of the ***symptoms of CFS/ME***
***or that it is strongly associated with another important etiologic factor.***

[Summarizes Lerner et al 1993 report of abnormal T-waves, abnormal left ventricular myocardial dynamics, decreased and/or flat ejection fractions with stress, abnormal wall motion at rest and stress, dilatation of the left ventricle, and segmental wall motion abnormalities in CFS/ME patients].

We now report a subset of CFS/ME patients with (1) high human cytomegalovirus (HCMV) IgG enzyme-linked immunoassay antibody titers (ELISA), (2)minimal or no serologic evidence of concurrent EBV multiplication, and (3) oscillating ECG abnormalities at Holter monitoring.

We performed a pilot study to assess the possible efficacy of ganciclovir, an antiviral nucleoside useful in the treatment of several HCMV infections in immunosuppressed patients.


DISCUSSION
This preliminary open trial of IV ganciclovir in patients with CFS/ME, abnormal T-wave oscillations at Holter monitoring, and significant HCMV ELISA antibody titers was conducted to identify a possible subset of patients who may benefit from this therapy.

A significant HCMV ELISA IgG antibody titer (>120 U) with or without the presence of an HCMV IgG antibody titer, plus an absence of EBV VCA IgM antibody titer, along with an EBV EA antibody titer of <40 may help describe a CFS/ME cohort of patients who may derive benefit from ganciclovir. This study as not blinded, randomized, or placebo-controlled, and the efficacy of ganciclovir has not been determined. The use of a single 30-day course of intravenous ganciclovir is arbitrary.

During the EBV infectious cycle, antigen is expressed and can be divided into a diffuse (EA-D) complex and a cytoplasmic restricted (EA-R) complex. Here, we assayed EA-D. The 52/50 kDa EA-D protein complex neutralizes EBV-encoded DNA polymerase activity. Elevated EBV VCA IgM and EBV EA antibody titers indicate recent EBV multiplication (e.g., within 90 days). Buffy coats from blood samples, urine samples, and cardiac biopsies did not contain infectious HCMV. It appears that we report a nonlytic, nonpermissive, persistent HCMV infection.