The Hummingbirds' Foundation for M.E.

The Hummingbirds' Foundation for M.E. (HFME) is fighting for the recognition of M.E.,
and for patients to be accorded the same basic human rights as those with similar
disabling and potentially fatal neurological diseases such as M.S.

Articles sorted by author: Dr Lerner

An important note:

Before reading this research/advocacy information given in the links below, please be aware of the following facts:

1. Myalgic Encephalomyelitis and ‘Chronic Fatigue Syndrome’ are not synonymous terms. The overwhelming majority of research on ‘CFS’ or ‘CFIDS’ or ‘ME/CFS’ or ‘CFS/ME’ or ‘ICD-CFS’ does not involve M.E. patients and is not relevant in any way to M.E. patients. If the M.E. community were to reject all ‘CFS’ labelled research as ‘only relating to ‘CFS’ patients’ (including research which describes those abnormalities/characteristics unique to M.E. patients), however, this would seem to support the myth that ‘CFS’ is just a ‘watered down’ definition of M.E. and that M.E. and ‘CFS’ are virtually the same thing and share many characteristics.

A very small number of ‘CFS’ studies refer in part to people with M.E. but it may not always be clear which parts refer to M.E. The
A warning on ‘CFS’ and ‘ME/CFS’ research and advocacy paper is recommended reading and includes a checklist to help readers assess the relevance of individual ‘CFS’ studies to M.E. (if any) and explains some of the problems with this heterogeneous and skewed research.

In future, it is essential that M.E. research again be conducted using only M.E. defined patients and using only the term M.E. The bogus, financially-motivated disease category of ‘CFS’ must be abandoned.

2. The research referred to on this website varies considerably in quality. Some is of a high scientific standard and relates wholly to M.E. and uses the correct terminology. Other studies are included which may only have partial or minor possible relevance to M.E., use unscientific terms/concepts such as ‘CFS,’ ‘ME/CFS,’ ‘CFS/ME,’ ‘CFIDS’ or Myalgic ‘Encephalopathy’ and also include a significant amount of misinformation. Before reading this research it is also essential that the reader be aware of the most commonly used ‘CFS’ propaganda, as explained in A warning on ‘CFS’ and ‘ME/CFS’ research and advocacy and in more detail in Putting research and articles on Myalgic Encephalomyelitis into context.

Unfortunately the author featured on this page (Dr Lerner) mixes together many of the facts of M.E. and 'CFS' and uses the terminology incorrectly and confusingly.

While terms such as 'CFS' and 'ME/CFS' are used by Dr Lerner, it is certain that at least part of his research relates to authentic M.E. patients - although it should also be noted that mononucleosis/glandular fever and the EBV virus (and the CMV virus) have been comprehensively disproven with regards to causing M.E. for more than 15 years. M.E. is unequivocally NOT caused by EBV and this is supported by an abundance of scientific evidence. An enterovirus is the type of virus which is the most likely culprit for M.E. for a number of compelling reasons, see The outbreaks (and infectious nature) of M.E. section for more information.

(Note also that while cardiac abnormalities in 'CFS' may be a newly discovered phenomenon, cardiac abnormalities have been documented in M.E. since the earliest outbreaks.)

It is important that readers are aware that the HFME not only does not support referring to M.E. as 'CFS' or 'ME/CFS' or the mixing of facts relating to M.E. and 'CFS' etc. but is in fact actively involved in campaigning against such problematic concepts, for the benefit of all patient groups involved. 

Artciles by Dr Lerner

RESEARCH BREAKTHROUGH: ME/CFS AN INFECTIOUS CARDIOMYOPATHY? by: Philipa D. Corning, Ph.D., B.Sc. (Reviewed and approved by Dr. A. Martin Lerner)

In this study, 100% of the ME/CFS participants showed abnormal oscillating T-waves at 24 hr. holter monitoring and 24% showed weakened function on the left side of the heart (abnormal cardiac dynamics). This is the side of the heart that pumps oxygenated blood to all of the body, except the lungs. Data, gathered from biopsies and a 24-hour electrocardiogram (EKG) Holter monitor, showed that patients exhibited evidence of cardiomyopathy or disease of muscle in the heart.

These researchers tracked EKGs over a 24-hour period with a Holter monitor device and documented abnormal T-waves. This wave measures electrical recovery after contraction of the left ventricle. A normal T-wave should be shaped like the rolling crest of a wave in water. In 100% of ME/CFS patients, Lerner and his associates documented T-wave Inversions and/or T-wave flattenings. This finding is so consistent, they suggest that the Holter results should be included as part of the CDC case definition; it distinguishes ME/CFS patients from those with fatigue or unexplained origin. This research holds the potential to distinguish ME/CFS patients from FM patients, from those with other pain syndromes who do not relapse with exertion, and from those with fatigue associated with depression, which is a group that also does not suffer relapse with exertion. This work offers hard evidence to back up ME/CFS patients' much disbelieved claim that exercise is harmful and causes disease progression in ME/CFS.

In Dr. Lerner's model, the weakened heart is aggravated by physical activity, accounting for the post-exertional sickness and accounting for the post-exertional sickness so common in this disease - including flu symptoms, chills, fevers and increasing weakness. Indeed, the cardiac connection is what is so ground-breaking about this research.

In experiments with mice, Dr. Lerner has shown that raised myocardial coxsackie viral titers accompany physical exertion in the mice. When the heart muscle tissue is infected, overactivity causes death of cardiac tissue and disease progression. This is in direct conflict with the U.S. government research conclusions that ME/CFS disease symptoms are caused by underactivity due to a sedentary lifestyle. Dr. Lerner advises resting the heart in order to "do no harm" and to prevent death of cardiac tissue.

Dr. Lerner and associates also have documented abnormal ejection fractions in ME/CFS. Normally, over half of the blood in the left ventricle is ejected when the left ventricle contracts (part of the heart that pumps oxygenated blood out to the body). In Dr. Lerner's ME/CFS subjects, the ejection fraction is sometimes decreased, an indication that not all the normally-expelled blood leaves the ventricle. Some patients had reduced ejection fractions at rest while others had an ejection fraction that decreased during exercise from 51% to 36%. In a normal subject, the ejection fraction will rise over 5% during exercise. Stationary or falling ejection fraction is abnormal in coronary artery disease or cardiac muscle disease. Declining ejection fractions are not seen in normal persons leading sedentary lives.

These cardiac abnormalities are hypothesized to be virally induced.

This model explains the John Hopkins' finding of Rowe et al in which ME/CFS patients exhibited abnormal response to upright tilt. Lerner argues that it is abnormal cardiac response of cardiomyopathy instead of abnormal neural response. Indeed, Dr. Lerner's thesis explains a myriad of phenomenon that other research has not. For example, it explains why patients relapse with exertion and why only physically active young persons may acquire the disease. It also explains why stress is a major aggravator in this disorder. Stress may aggravate both herpes viruses and heart conditions. It also explains the anti-viral lymphocyte enzyme system, the 2-5 A pathway, suggesting the presence of a chronic infection.

In short, Dr. Lerner's work explains why previously healthy, vigorous young adults fall ill with chronic cardiomyopathy due to viral infection and cannot exercise for fear of causing further heart damage. This is directly opposite to the work of Dr. Stephen Straus at National Institute of Health (NIH) whose theory states that ME/CFS is a psychiatric disorder. This new research of Dr. Lerner et al is both refreshing and insightful. Needless to say, it has also been long awaited.

See also: Chronic Fatigue Syndrome May Be An Infectious Cardiomyopathy Of Single Or Multiple Viral Etiology by Maryann Spurgin, Ph.D.

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. 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.

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.

Lay Summaries of Published Peer-Reviewed Studies from Dr Martin Lerners Website:

Repetitively negative changing T-waves at 24-h electrocardiographic monitors in patients with the chronic fatigue syndrome (left ventricular dysfunction in a cohort). Lerner AM, Lawrie C, Dworkin HJ. Chest. 1993;104:1417-1421.

Here, we showed that 24 CFS patients have abnormal cardiac electrical conduction by 24-Hr. ECG testing (Holter monitoring) compared to 106 non-fatigued control patients (p<0.03). In 8 of the 24 CFS patients, gross abnormal cardiac wall motion at exercise MUGA testing was seen. Coronary artery disease was excluded by myocardial perfusion imaging in all CFS patients.

This was our first publication in continuing studies of the chronic fatigue syndrome. Here, for the first time, cardiac abnormalities in CFS illness were recognized.

"Cardiac involvement in patients with chronic fatigue syndrome as documented with Holter and biopsy data in Birmingham, Michigan, 1991-1993." Lerner AM, Goldstein J, Chang CH et al.  Infectious Diseases in Clinical Practice 1997;6:327-33.

Here, the prevalence of abnormal Holter monitoring in 67 CFS patients and 78 non-CFS patients matched for age, place and time and absence of other confouding medical diseases were compared. Holter monitors in both CFS and control groups were read by two non-involved cardiologists without clinical knowledge about the patient or place in the study. Dr. Lerner was not a reader of Holter monitors in this study. The prevalence of T-wave abnormalities by Holter monitoring was greater in CFS than in non-CFS patients (p<0.01). The presence of abnormal T-waves at Holter monitoring was "a sensitive indicator of the presence of CFS." The "absence" of these abnormal T-waves made the diagnosis of CFS unlikely (statistical sensitivity 0.96). Light and electron micrographic studies of right ventricular endomyocardial biopsies in these CFS patients showed cardiomyopathic changes. We do not recommend further right ventricular cardiac biopsies in CFS patients since the hearts of CFS patients may be friable and may have an increased likelihood of post-biopsy bleeding.

Summary of Publications 1-3 (Cardiac Involvement in CFS)

This work shows that rapid heart rates at rest, and in some cases, abnormal cardiac wall motion contribute to the light-headedness that many CFS patients experience. Uniformly, abnormal Holter monitoring is present in CFS patients. This additional criterion for diagnosis of CFS illness, namely abnormal Holter monitoring, to the CDC criteria for the diagnosis of CFS does not exclude any CFS patients included in the original CDC definition. The absence of abnormal Holter ECG testing excludes fatigued patients who do not have CFS.A unified theory of the cause of chronic fatigue syndrome. Lerner AM, Zervos M, Dworkin HJ, Chang, CH and O'Neill W. Infectious Diseases in Clinical Practice 1997;6:230-243.

Here, we hypothesize that CFS is a prolonged infectious mononucleosis syndrome in previously healthy (immunocompetent) persons. We further speculate in this early study that prime candidates for cause of CFS are two herpesviruses which cause infectious mononucleosis, Epstein-Barr virus (EBV) and cytomegalovirus (HCMV). We further suggest that studies seeking a single virus cause of CFS, even those studies searching for single-virus EBV or single virus HCMV would conclude in a result of "no cause". Indeed, such negative studies have been done. We suggest that (1997) there may be three causes of CFS, 1) single virus, EBV CFS; 2) single virus HCMV CFS; and 3) EBV-HCMV co-infection CFS. We outline research studies to prove or disprove this new paradigm.\

Editorial response: microbial persistence and idiopathic dilated cardiomyopathy. Lerner AM. Clinical Infectious Diseases. 1999;29:526-7.

Here, Dr. Lerner discusses the possible relationship between long-standing cardiomyopathy, heart muscle disease not associated with coronary artery disease, and CFS.

"New cardiomyopathy: a pilot study of intravenous gancyclovir in a subset of the chronic fatigue syndrome." Lerner AM, Zervos M and Dworkin HJ et al. Infectious Diseases In Clinical Practice 1997;6:110-117.

Here, we emphasize the need of subset classification in the diagnosis and treatment of CFS illness. CFS patients in this study had significant IgG serum antibody titers to cytomegalovirus, but little to no evidence of EBV infection by blood tests. In this study 13 of 18 CFS patients were remarkably improved after 30 days of intravenous ganciclovir (p<0.05). Single virus HCMV CFS in this pilot study was improved by antiviral treatment. There were no side effects from this carefully monitored trial.

A six-month trial of valacyclovir in the Epstein-Barr virus subset of chronic fatigue syndrome: improvement in left ventricular function. Lerner AM, Beqaj SH, and Deeter RG et al.  Drugs of Today. 2002;38:549-561.Drugs of Today. 2002;38:549-561.

Twenty-five patients with CFS illness were treated orally for 6 months with pharmacokinetic doses of valacyclovir (valtrex) in a formulation to give continuous anti-EBV effective blood levels throughout the day. This is the first time such valacyclovir dosing was given. The trial was approved by the U.S. Food and Drug Administration. Patients were carefully monitored for safety by repeated appropriate blood tests. There were no adverse side effects. Sixteen patients with single virus EBV infection were benefitted, but 9 clinically similar CFS patients with EBV-HCMV co-infection were not benefitted. Valacyclovir (valtrex) in the laboratory is effective versus EBV, but it is NOT effective (active) versus HCMV. Therefore, the results strengthen the need for subset classification and appropriate subset-directed antiviral treatment for CFS illness. This, to our knowledge, is the first successful report of valacyclovir treatment for EBV infection.

A small, randomized, placebo-controlled trial of the use of antiviral therapy for patients with chronic fatigue syndrome. Lerner AM, Zervos M and Chang CH et al. Clinical Infectious Diseases. 2001;32:1657-58.

Eleven CFS patients with EBV-HCMV co-infections were appropriately treated according to their prior subset classification over an 18-month period with antiviral drug treatments. All patients were carefully monitored for safety every 4-6 weeks. Valacyclovir for EBV infection and ganciclovir for HCMV infection were used. There were no significant side effects in CFS patients. All 11 CFS patients in this study were significantly improved.

Summation of Publications 4, 6-8 (Treatment of CFS Illness with Anti-viral Drugs According to Subset Classification)

In these studies, 40 CFS patients were safely treated with antiviral drugs. They were remarkably improved.

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. Lerner AM, Beqaj SH, Deeter RG and Fitzgerald JT.  In Vivo. 2002;16:153-160.

This is an especially enlightening study. In many CFS patients in whom our work implies an A) EBV; B) HCMV; or C) EBV-HCMV (co-infection) cause for CFS illness, normal means for diagnosis by blood tests or virus isolation (including those using polymerase chain reactions) are negative, both in our work, reviewed here, and in the careful work of others. In this study, we show a definitive new means of HCMV multiplication in this HCMV subset of CFS patients. The p52 and CM2 HCMV IgM antibodies were present in 16 CFS patients, but were not present in 77 various control patients. In these CFS patients, portions of the HCMV genetic material are synthesized, but remain unassembled into complete virus. These data provide strong evidence for a virus etiology for CFS illness and provide a strong rational for antiviral treatment of CFS patients.

"Cardiac and virologic issues" pp 304-330 from Handbook of Chronic Fatigue Syndrome. Lerner AM, Deeter RG, O’Neill W, Dworkin HJ, Zervos M, Beqaj SH, Chang CH, and Fitzgerald JT. Jason LA, Fennell PA, and Taylor RR. John Wiley & Sons, Inc. 2003.

We present the evolution of data describing studies over greater than a decade which support the paradigm that CFS is a prolonged infectious mononucleosis due to Epstein-Barr virus, cytomegalovirus or the two viruses in co-infection undergoing incomplete virus multiplication. The paradigm suggests that the immunocompetent (otherwise healthy) CFS patients' immune defenses do not allow complete virus formation, but only parts of the virus(es) genetic material is expressed. Cardiac involvement of this newly hypothesized method of virus infection leads to rapid heart pumping at rest (tachycardia) and eventually cardiac muscle pump weakening. Specific antiviral treatment has led to remarkable sustained improvement in patient well being so that criteria for the diagnosis of CFS are no longer present. Medical testing by Holter monitoring, MUGA, nuclear stress testing, cardiac biopsy, virus serologic tests and disappearance of symptoms of CFS support this theory.

IgM serum antibodies to Epstein-Barr Virus are uniquely present in a subset of patients with the chronic fatigue syndrome. Lerner AM, Beqaj S, Deeter RG, and Fitzgerald JT.  In Vivo. 2004;18:101-106.

A first unique subset of patients with chronic fatigue syndrome (CFS) and specific diagnostic serum antibodies to cytomegalovirus (HCMV) non-structural gene products p 52 and CM2 (UL 44 and UL 57) indicates incomplete HCMV persistent multiplication in these specific patients with CFS. The results suggest that specific antiviral (HCMV) treatment in these patients may be beneficial. A second Epstein-Barr Virus (EBV) distinct subset of CFS is now defined. Fifty-eight CFS patients and 68 non-CFS matched controls were studied. Serum antibodies to EBV viral capsid antigen (VCA) IgM and EBV Early Antigen, diffuse (EA, D) as well as HCMV (V), IgM and IgG; VP (sucrose density purified V); p 52 and CM2, IgM serum antibodies were assayed. Serum EBV VCA IgM positive antibody titers were identified in 33 CFS patients (Group A subset EBV VCA IgM 62.3 ± 8.3, neg < 20), but were not present in other CFS patients (Group B subset EBV VCA IgM 6.8 ± 0.7) or controls (p < 0.0001). EBV VCA IgM titers remained positive in CFS patients from Group A for 24-42 months. Anti-viral medicines effective in HCMV and EBV infections are different, and preliminary studies suggest that this patient-specific pharmacokinetically directed antiviral therapy should be continued for 6-12 months. Trials of antiviral therapy must be individually monitored by complete blood counts, creatinine and tests of liver function (AST, ALT) every 4-6 weeks for safety. (reference publication #7)

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. Lerner AM, Dworkin HJ, Sayyed T, Chang CH, Fitzgerald JT, Beqaj S, Deeter RG, Goldstein J, Gottipolu P and O'Neill W.  In Vivo. 2004;18:417-424.

Here, we report a prospective consecutive case control study from 1987-1999 of cardiac dynamics as measured by radionuclide, ventriculography in 98 CFS patients. Controls were 191 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 of 87 patients (11.5%). With stress exercise, 21 CFS patients (24.1%) demonstrated ACWM. Cardiac biopsies in 3 CFS patients with ACWM showed a cardiomyopathy. Among the controls, ACWM at rest was present in 4 of 191 patients (2%) (p=0.0018). A progressive cardiomyopathy often associated with EBV and/or HCMV incomplete virus multiplication is present in CFS patients.

Abnormal left ventricular myocardial dynamics in eleven patients with chronic fatigue syndrome. Dworkin HJ, Lawrie C, Bohdiewicz P, Lerner AM. Clinical Nuclear Medicine 1994; 19(8): 675-7.

Abstract: Eleven patients diagnosed with chronic fatigue syndrome were found to have abnormal left ventricular myocardial dynamics as indicated on MUGA studies. Among the abnormalities noted were low EF at rest or stress (3/11), dilatation of the left ventricle (5/11), and segmental wall motion abnormalities (7/11). One patient had elevated CPK and flat EF response to exercise.