What is your approach to treating patients with CFS?

What tests do you perform to diagnose and monitor CFS? 

Once diagnosed, what are the current treatment options for CFS?

What is your most current research on CFS?

What is your approach to treating patients with CFS?

After nearly 20 years in academia, Dr. Lerner began an Internal Medicine and Infectious diseases practice in 1982.  His background was Infectious Diseases, particularly viral diseases, and he was aware of virus induced heart disease, having studied this in his university research.  Soon after beginning his practice, Dr. Lerner noticed that the symptoms of CFS resembled a prolonged infectious mononucleosis.  Infectious mononucleosis may be caused by one of two herpesviruses: the Epstein-Barr virus (EBV) or the Human Cytomegalovirus (HCMV).  These two mononucleosis syndromes are self-limited; that is, patients recover.

Dr. Lerner began to question… Could the Chronic Fatigue Syndrome be a prolonged mononucleosis syndrome?  There isn’t anyone who has any kind of a heart condition who isn’t fatigued.  Could the Chronic Fatigue Syndrome also involve the heart?

He began to look at patients with CFS for evidence of involvement of the heart, and the two mononucleosis viruses (EBV) and HCMV).  The findings have been remarkable!

A.  Abnormal Holter Monitoring

Abnormal T-wave flattenings and inversions are found in patients with the US Centers for Disease Control defined CFS.  This finding has been tested statistically, and we can now say that 90% of patients with CFS have abnormal 24-hour monitoring.  This is a biomarker.  The absence of abnormal Holter monitoring leads us to believe that CFS as the cause of fatigue is less likely.  The T-wave of the electrocardiogram records repolarization (electrical recovery) of the left ventricle after every heartbeat in preparation for the next heartbeat.  The normal T-wave is upright.  With increased heart rates the abnormal T-waves occur.  Abnormal oscillating T-waves occur with exercise.  The symptoms of CFS are worsened by exercise, a striking coincidence.
   

B.  Abnormal Contraction of the Heart

Patients with CFS who have been ill for months may have abnormal cardiac dynamics.  This means that the rhythmic, symmetrical, wonderful symphonic-like harmonious closure of the left ventricle is now asymmetric.  This indicates that there is some weakening of the left ventricular muscle.  (Patients with coronary artery disease may also have abnormal left ventricular dynamics.)  We have found that approximately 1 in 4 patients with CFS who has been ill for one year or more has abnormal asymmetric abnormal cardiac dynamics.  It is indeed frightening to hear of weakening of the heart muscle.  Therefore, at this time and out of context, I report that the treatment with anti-viral medicines, which we use, may reverse this heart muscle weakness, and return it toward normal!

C.  Heart Biopsies Show Cardiomyopathy

Biopsies of the heart from CFS patients indicate that there is cardiac involvement.  I have been fortunate to attract a very talented group of physicians interested in studying CFS with me.  They are Dr. Howard Dworkin, formerly Head of Nuclear Medicine at William Beaumont Hospital (WBH); Dr. William O’Neill, formerly Head of Cardiology ,WBH, and presently Clinical Dean, University of Miami School of Medicine; Dr. James Goldstein, Academic Cardiologist, WBH,  and Dr. Marcus Zervos, formerly Head of Infectious Diseases Research, WBH, now Chief, Infectious Diseases, Henry Ford Hospital, Detroit.  Thomas Fitzgerald, Ph.D., Statistician on the faculty of the University of Michigan Hospital has been and is a continuing important collaborator.  Sio Beqaj, Ph.D, molecular biologist, currently Director of Path Group Laboratory, Nashville, TN, has been and remains an active collaborator.  He is also Director of the laboratory at the Treatment Center for CFS, Beverly Hills, MI.  Robert G. Deeter, Ph.D., formerly of Anti-Infectives, GlaxoWelcome Co., now at AmGen Laboratory, California, was an active collaborator.  In addition, Dr. C.H. Chang, Anatomic Pathology, WBH, has done special staining and electron microscopic studies of cardiac biopsies of CFS patients.

D.  Viruses

There is firm evidence in CFS patients that active Epstein-Barr virus (EBV), active cytomegalovirus (HCMV), active Human Herpesvirus 6 or a combination of these viruses, are common findings in patients with CFS.  In 1997, Dr. Lerner hypothesized CFS is caused by 3 herpesviruses: EBV, HCMV and/or HHV6. These three viruses establish “latent” infection in B-lymphocytes, monocyte-macrophage precursors, or T-lymphocytes respectively.  Virus reactivation, and both abortive and complete virus multiplication occur.  Therefore CFS patients have been described with continuing primary or reactivated infections.

E.  Treatment

In a controlled pilot study (random and blinded) the antiviral drug valacyclovir (Valtrex) is shown effective in reducing the fatigue of single virus EBV CFS.  A blinded trial of valacyclovir has been completed and confirms the original study.  Initial studies involving subsets including HCMV and HHV6, utilizing the antiviral drug valgancyclovir (Valcyte), are also successful and exciting.  When patients are treated with appropriate antiviral medicines after specific proof of EBV, HCMV and/or HHV6 virus active infection (subset classification), research has shown significant improvement in cardiac and CFS symptoms. 

What diagnostic approach do you take to establish, and then monitor CFS? 

Initial patient overview:

Complete history, physical examination, chest X-ray, electrocardiogram, complete blood count, urinalysis, serum aspartate and aminotransferases (AST, ALT), glucose, thyroid stimulating hormone, sodium, potassium, uric acid, alkaline phosphatase and creatinine measurements were performed.

CFS analysis:

Energy Index Point Score® assessing physical functional capacity in activities of daily life documenting limitations

Cardiac testing:

24-hour Holter monitor - symptoms recorded (syncope, chest pain, palpitations, muscle aches)

Standard 12-lead resting electrocardiogram

Rest/stress myocardial perfusion study

Multigated (radionuclide) MUGA rest/stress ventriculographic examination

Viral testing for EBV, HCMV, HHV6:

EBV serum IgM viral capsid antibodies (VCA) - Diasorin, Inc., Stillwater, MN

EBV early antigen diffuse (EA) - Diasorin, Inc., Stillwater, MN

ELISA HCMV(V) IgG and IgM serum antibodies to viral capsid, strain 169 HCMV - Diasorin, Inc., Stillwater, MN

HHV6 IgM and IgG serum - Lab Corp, Dublin, OH

Co-infection testing:

ELISA and Western blot to Borrelia burgdorferi (IgM and IgG) - Lab Corp, Dublin, OH

IgM and IgG of Babesia microti - Lab Corp, Dublin, OH

IgM and IgG of Anaplasma phagocytophila - Lab Corp, Dublin, OH

IgM and IgG of Mycoplasma pneumoniae - Lab Corp, Dublin, OH

Anti-streptolysin O (ASO) titer <400 units - Lab Corp, Dublin, OH

Follow-up:

Every 4-6 weeks - Complete blood counts, sodium, potassium, AST, ALT, alkaline phosphatase, creatinine and urinalysis.

Every 3 months – Serum assays for EBV VCA IgM, EBV EA, HCMV(V) IgM and IgG, HHV6 IgM and IgG

Source: Lerner AM, Beqaj SH, Deeter RG, Fitzgerald JT. Valacyclovir treatment in Epstein-Barr virus subset chronic fatigue syndrome: thirty-six months follow-up. In Vivo. 2007 Sep-Oct;21(5):707-13.

Once diagnosed, what are the current treatment options for CFS?

In a controlled pilot study (random and blinded) the antiviral drug valacyclovir (Valtrex) is shown effective in reducing the fatigue of single virus EBV CFS.  A blinded trial of valacyclovir has been completed and confirms the original study.  Initial studies involving subsets including CMV and HHV6, utilizing the antiviral drug valgancyclovir (Valcyte), are also successful and exciting.  When patients are treated with appropriate antiviral medicines after specific proof of EBV, CMV and/or HHV6 virus active infection (subset classification), research has shown significant improvement in CFS symptoms.  Please note success of treatment is based on the exclusion of the noted co-infections under co-infection testing above.  Should a co-infection also be present, it must be treated in addition to the herpesvirus CFS for any improvement to occur.

What is your most current research on CFS?

The most recent, and most groundbreaking, piece of research to date is in its final stages of publication submission.  However some of the initial findings were presented at the 8th International IACFS Conference on Chronic Fatigue Syndrome, Fibromyalgia and other related Illnesses January 12-14, 2007, Fort Lauderdale, Fla.

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