Dr. Martin Lerner's Treatment Protocol for ME/CFS

Dr. Martin Lerner has been a long-time proponent of antiviral therapies for treating ME/CFS. His background as an infectious disease specialist naturally led him to explore antimicrobials because he believes that microbial infections lie at the heart of ME/CFS symptomatology. He has authored numerous papers on antiviral treatments for ME/CFS, and has treated patients for decades.

Below is his guide to treating patients with ME/CFS using antimicrobial agents. He also includes the roster of tests he uses for diagnosis, and a section on patient care.

Dr. Lerner makes the disclaimer that his guide has not been peer-reviewed, but that does not make it any less valid. The guide is a summary of decades of clinical experience and, as such, stands on its own.

You can read the original document here:

http://www.treatmentcenterforcfs.com/documents/MECFSTreatmentResourceGuideforPractitioners.pdf

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DISCLAIMER: The information contained in this document is meant for informational purposes only. The management of ME/CFS in any given patient must be approached on an individual basis using an Infectious Diseases’ specialist’s best judgment. This document is a culmination of over 20 years of ME/CFS practice and peer reviewed articles. This document is not a peer reviewed publication.

ME/CFS Treatment Resource Guide for Practitioners

By A. Martin Lerner, M.D., M.A.C.P.

Beaumont Health System Treatment Center for Chronic Fatigue Syndrome

Diagnostic Methodology

Initial patient visit:

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 performed.

ME/CFS analysis:

Energy Index Point Score® assessing physical functional capacity in activities of daily life documenting limitations. The EIPS® system defines the severity of patient fatigue, 0-10, through measurement of real-life situations including one’s ability to sit, stand, be out of bed, work, perform housework, socialize, exercise. The EIPS® level is determined through discussion between the physician and patient. A change in EIPS® level of one is a significant change in health and lifestyle for the patient, as ME/CFS symptoms decrease when the EIPS® increases.

Cardiac testing:

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

–Standard 12-lead resting electrocardiogram – if original ECG abnormal

–Rest/stress myocardial perfusion study – if original ECG abnormal

–Multigated (radionuclide) MUGA rest/stress ventriculographic examination – if original ECG abnormal

–Monitor Blood Pressure (laying, sitting, standing)

–Monitor Heart Rate (laying, sitting, standing)

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:

–Western blot and ELISA 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

Note Lyme and Lyme co-infections can be elusive. Lyme disease can present clinically as ME/CFS. A significant portion of Lyme disease cases have negative Lyme serologic tests. We prefer Lab Corp for Lyme testing and use all 4 tests. The antigens used are those used by the CDC. An appropriate rural exposure, a tick bite, a bull’s eye rash, can all add to the likelihood of Lyme disease. Due to the need for both clinical and diagnostic evaluation in Lyme disease, it is recommended to consider an Equivocal (not negative or positive) lab result, as positive and begin Lyme treatment.

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 and all co-infections which are positive originally

EIPS® - A Functional Capacity Measurement Tool For Chronic Fatigue Syndrome (CFS) Patients

To Physicians Caring for Patients with CFS

The Energy Index Point Score (EIPS) chart provides the severity of patient fatigue. A change in EIPS level of one is a large significant change. The EIPS level is determined by agreement of physician and patient with the EIPS chart easily available for viewing at out-patient visits. As the EIPS level increases, CFS symptoms lessen and disappear.

How to use the EIPS system in four easy steps:

1) Post the EIPS chart in examining room

2) Ask patient to evaluate their level of activity based upon the prior two weeks

3) Question the patient’s EIPS evaluation

4) Record and track the EIPS level. Report every 6-12 weeks.*

* The EIPS is not assessed if the patient has an intercurrent infection (respiratory, gastroenteral, ...). At the same visit the following 4 symptoms are regularly categorized: 1) chest pain 2) palpitations 3) muscle aches 4) lightheadedness - noting whether absent or present. If present, when (beginning or end of day, how frequent), where, severity, etc. All of these factors are included in the EIPS assessment.

Antiviral Treatment of EBV

General Information

A diagnosis of Epstein-Barr virus(EBV) infection is made with a positive EBV EA antibody diffuse and/or a positive VCA IgM antibody.

Treatment

Valacyclovir (Valtrex) is remarkably effective and safe. The one concern is that valacyclovir is excreted by the glomerulus and secreted by the tubules and can cause acyclovir stones and obstructive uropathy. This will not occur if the patient drinks at least six 8-ounce glasses of water daily. Occasionally diarrhea may be caused by the valacyclovir. If the patient weighs 70 kg, the dosage is 1 gram four times daily, ideally every six hours; however safe to take four hours after the last dosage (it is not necessary to awake in the middle of the night for a dose). It is important that the patient take four doses for treatment. A higher dose of Valtrex may be necessary with patients who weigh more than 175 pounds and this must be done carefully. A patient who weighs more than 175 pounds may require 1.5 grams of Valtrex, valacyclovir four times daily. Please note valacyclovir is now available in generic form. While I have not had experience with all distributors of generic forms yet, I have had patients move to the generic form of valacyclovir by Teva and Mylan with no issue.

Famvir at the same dosage can be substituted and although there is not the strong evidence that we have for valacyclovir, it likely is equally effective. One does not have the worries concerning renal calculi with Famvir and it has also been extraordinarily safe. It does not cause diarrhea.

An initial worsening of symptoms with normal laboratory at a two-week special visit with worsening symptoms is a Jarisch Herxheimer reaction and predicts a good response. Initial benefit is usually not noted for the first six weeks’ of therapy and then occurs thereafter. A minimum period of therapy is one year. Usually benefit is not apparent until after 3.5 months of therapy.

We have not seen thrombocytopenia with Valtrex, valacyclovir. However, an elevated mean corpuscular volume is seen. This is not a toxicity, and does not require one to stop medicines.

Antiviral Treatment of HCMV & HHV6

General Information

A diagnosis of cytomegalovirus(CMV) infection is made with an elevated CMV IgG titer. The IgM titer for CMV is inaccurate and insensitive. The higher the CMV IgG titer, the greater the viral load. Human herpes virus 6 infection is made with an elevated titer at least twice normal. The diagnosis of EBV, CMV, or HHV6 ME/CFS meets the Canadian consensus and Fukuda CFS criteria.

Treatment

The usual treatment for either/both is valganciclovir (Valcyte) one 450-mg capsule daily for three days, followed by two 450-mg capsules in the morning daily. Liver function tests are studied very carefully. If there is any abnormality, one alters the dosage. Given the patient’s ability to safely tolerate two 450-mg capsules, dosing can be increased to two, 450-mg capsules in the morning and a one additional 450-mg capsule twelve hours later. Liver function tests, again, must be studied carefully and frequently.

Both valacyclovir and valganciclovir are absorbed with a 20% increment if there is food in the stomach. The most common side effect of valganciclovir is hepatotoxicity. If this occurs, the drug is stopped, the dosage is decreased, and is again restarted. When monitoring reveals AST and ALT are normal, the monitoring can continue every four to six weeks, but more frequent with hepatotoxicity. The rule is no valganciclovir at all if there is any abnormality in liver function.

The duration of valganciclovir and therapy for CMV and/or HHV6 is aimed at one year to start with no improvement expected for the first four to six months. It is a general rule that the shorter the duration of ME/CFS, and the earlier appropriate therapy is started, the earlier recovery will occur. Recovery is a continuing, gradual process.

We have not seen thrombocytopenia with Valcyte, valganciclovir. An elevated mean corpuscular volume is seen. This is not a toxicity to stop medicines.

Antibiotic Treatment of Co-infections

Background

If the diagnosis of ME/CFS is made by the accepted criteria and there is no coinfection, one begins antiviral therapy promptly. However, if there is coinfection with a diagnosis of Lyme disease, Babesiosis, Ehrlichiosis, Mycoplasma pneumoniae, or adult rheumatic fever, these conditions are addressed first. After these conditions are addressed, ME/CFS is treated with antiviral therapy. Should one or more of these co-infections occur mid- antiviral treatment, do not stop but treat in parallel.

Treatment of Lyme Disease

The protocol for Lyme disease, serologically positive or epidemiologically positive and serologically negative, that I use is a six-week’s course of intravenous therapy. Ceftriaxone is preferred. If there is a history of allergy to penicillins and it is not an immediate allergy, I routinely refer the patient to an allergist for cephalosporin testing. Under ordinary circumstances if this is negative, ceftriaxone is given; depending on the size of the individual 1-1.5 grams intravenously every 12 hours. The patient is seen weekly. They are asked not to travel further than 45 minutes from this office, because a PICC lines has been placed and infection of the PICC line site or side effects to the cephalosporin can occur; particularly biliary dyskinesia or abnormal liver function tests with ceftriaxone. Cefotaxime may be substituted for ceftriaxone in the case of biliary dyskinesia. If there is biliary dyskinesia, Unasyn, or ertapenem may be used. If diagnosis of Lyme occurs after antiviral treatment has commenced, and patient shows liver sensitivities with Valcyte dosing, Unasyn is recommended. Unasyn is given 2 grams IV piggyback every 12 hours. Ertapenem is given 2 grams IV piggyback every 24 hours. The same dosage of cefotaxime (as ceftriaxone) of 1-1.5 grams is used, but the administration of cefotaxime IV is every 8 hours, rather than every 12 hours, for ceftriaxone. Cefotaxime has no hepatotoxicity. Cefotaxime is excreted by the kidneys.

The goal of Lyme therapy, of course, is a well patient, but particularly a negative serology. Oral suppressive therapy is continued for at least three months or until the Lyme serology is negative. Typical medicines used for Lyme suppression after the original six weeks are amoxicillin; in a 70-kg individual 750 mg before every meal and at bedtime. Doxycycline 100-150 mg twice daily after meals and with a full glass of water may be given in the place of amoxicillin for suppression.

Treatment of Mycoplasma Pneumonia

We use LabCorp less than 300 as a normal level. The patient is not considered to have persistent Mycoplasma pneumoniae infection unless the initial titer is 600 or more. Mycoplasma pneumoniae is treated intravenously with doxycycline 150 mg IV piggyback for six weeks followed by oral suppression with doxycycline 100-150 mg twice daily or moxifloxacin 400 mg once daily for three months. The goal of this therapy is a serum level which is less than twice the normal. The duration of time again is six weeks intravenously plus a minimum of three months oral suppression.

Treatment of Adult Rheumatic Fever

The diagnosis of adult rheumatic fever is made with an ASO titer of over 400. Echocardiograms are done in all patients with ME/CFS originally and any changes in the mitral valve, either thickening or mitral valve prolapse are additional supports for the diagnosis of adult rheumatic fever. A patient who meets the criteria for ME/CFS with an ASO titer of 400 or more is considered to have adult rheumatic fever and treated accordingly.

Chest pain, joint pain, rash, life-altering fatigue are all common to ME/CFS and adult rheumatic fever. Patients are diagnosed with adult rheumatic fever with the following criteria:

(1) EIPS <5

(2) Diffuse, multi-joint pain

(3) Antistreptolysin O titer ≥ 400 (critical to diagnosis)

(4) Abnormal 24 hour Holter monitor with tachycardia and oscillating T-wave flattening, with or without T-wave inversions

(5) A thickened mitral valve at echocardiogram.

If there are symptoms of sinus disease, a CT of the sinuses is done to make certain there is no obstructive sinusitis which may need sinus surgery.

Patients are treated with intravenous Unasyn 3grams IV piggyback every 12 hours for 4-6 weeks, followed by 2.4 million units IM (1.2 million units each hip every 30 days) until ASO titer is ≤200.

Patient Management

Patient Visits and Testing

Check-ups with labwork should occur every 6 weeks in-person.

Diet and Exercise

A healthy, well balanced diet is a must. Minimize sugar intake. Minimize caffeine intake. Absolutely no alcohol allowed, as it may be a cardiac toxin for ME/CFS patients.

No physical exertion or exercise until above a 7 Energy Index Point Score. Stretching regularly is recommended. Once the EIPS is 7, modest exercise can and should begin. The ultimate test is - Are you tired the next day after exercise? If you are, then the exercise that you have done is too much. Start out very slow. Just a few minutes, allowing for breaks and recovery time.

Lifestyle

10-12+ hours of sleep per day and daily naps until the EIPS is at least a 6. Avoid germs (think airplanes, libraries, churches). Stretch daily, minimize exertion, seek assistance with housework/chores/errands. Keep feet elevated, promote a network for assistance and ask for help. 

Daily energy envelope management is a must. Do not push until a crash. This is not productive. As much as possible, do not allow yourself to get overly tired. Healing is a slow process.

Publication Resources

•Lerner, A.M., Lawrie, C., Dworkin, H.S., and Fitzgerald, J.T.: Repetitively Negative Changing T-Waves at 24-Hour ElectrocardiographicMonitors In Patients With The Chronic Fatigue Syndrome: Left VentricularDysfunction In A Cohort. CHEST 104:1417-1421, 1993

•Dworkin, H.J., Lawrie, C., Bohdiewicz, P., and Lerner, A.M.: Abnormal Left Ventricular Myocardial Dynamics in Eleven Patients With TheChronic Fatigue Syndrome. Clinical Nuclear Medicine 19:675-677, 1994

•Lerner, A.M., Zervos, M., Dworkin, H., Chang, C.H., Fitzgerald, J.T., Goldstein, J., Lawrie-Hoppen, C., Franklin, B., Korotkin, S., Brodsky, M., Walsh, D., O’Neill, W.: New Cardiomyopathy: Pilot Study ofIntravenous Ganciclovir in a Subset of the Chronic Fatigue Syndrome. Infectious Diseases in Clinical Practice 6:110-117, 1997

•Lerner, A.M., Zervos, M., Dworkin, M., Chang, C.H., O’Neill, W.: A Unified Theory of the Cause of Chronic Fatigue Syndrome. Infectious Disease in Clinical Practice 6:239-243, 1997

•Lerner, A.M., Goldstein, J., Chang, C., Zervos, M., Fitzgerald, J., Dworkin, H., Lawrie-Hoppen, C., Korotkin, S., Brodsky, M., O’Neill, W.: Cardiac Involvement in Patients with Chronic Fatigue Syndrome asDocumented with Holter and Biopsy Data in Birmingham, Michigan, 1991-1993. Infectious Diseases in Clinical Practice 6:327-333, 1997

•Lerner, A M. Recurrent Herpes Simplex Virus Cellulitis ofthe Right Forearm with Early Elephantiasis Responsive to Both Treatment andProphylaxis by Valacyclovir. Infectious Diseases in Clinical Practice 8:260-262,1999

•Lerner, A.M., Beqaj, S.H., Deeter, R.G.: IgM antibodies tohuman cytomegalovirus nonstructural gene products p52 and CM2 (UL44 and UL57)are uniquely present in a subset of patients with chronic fatigue syndrome. In Vivo 16:153-160, 2002

•Lerner, A.M., Beqaj, S.H., Deeter, R.G., Dworkin, H.J., Zervos, M., Chang, C.H., Fitzgerald, J.T., Goldstein, J., and ONeil, W. Asix-month trial of valacyclovir in the Epstein-Barr virus subset of chronicfatigue syndrome improvement in left ventricular function. Drugs of Today 38 8:249-561, 2002

•Carruthers BM, Jain AK, DeMeirleir KL, Peterson DL, Klimas NG, Lerner AM, Bested AC, Flor-Henry P, Joshi P, Powles AC, Sherkey JA, van de Sande, MI. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Clinical WorkingCase Definition, Diagnostic and Treatment Protocols. Journal of Chronic Fatigue Syndrome 11 1:7-115, 2003

•Lerner AM, Beqaj SH, Deeter RG, Fitzgerald JT: IgM SerumAntibodies to Epstein-Barr Virus are Uniquely Present in a Subset of Patientswith the Chronic Fatigue Syndrome. In Vivo 18:101-106, 2004

• LernerAM, Dworkin HJ, Sayyed T, Chang CH, Fitzgerald JT, Beqaj S, Deeter RG, Goldstein J, Gottipolu P, O'Neill W: Prevalence of AbnormalCardiac Wall Motion in the Cardiomyopathy Associated with IncompleteMultiplication of Epstein-Barr Virus and/or Cytomegalovirus in Patients withChronic Fatigue Syndrome. In Vivo 18:417-424, 2004

Beqaj SH, Lerner AM, Fitzgerald JT: Immunoassay withcytomegalovirus early antigens from gene products p52 and CM2 (UL44 and UL57)detects active infection in patients with chronic fatigue syndrome. J Clin Pathology 61:623-626, 2008

•Lerner, Beqaj, Deeter, Fitzgerald. Valacyclovir treatmentin Epstein-Barr virus subset chronic fatigue syndrome: thirty-six monthsfollow-up. In Vivo 21(5): 707-713, 2007

•Lerner AM, Beqaj SH, Fitzgerald JT. Validation of theEnergy Index Point Score to Serially Measure the Degree of Disability inPatients with Chronic Fatigue Syndrome. In Vivo 22: 799-802, 2008

•Lerner AM, Beqaj SH, Fitzgerald JT, Gill K, Gill C, Edington J: Subset-directed antiviral treatment of 142 herpesvirus patientswith chronic fatigue syndrome. Virus Adaptation and Treatment 2010:2 47-57

•Lerner AM, Beqaj SH, Gill K, Edington J, Fitzgerald JT, Deeter RG: An Update on the management of glandular fever (infectiousmononucleosis) and its sequelae caused by Epstein-Barr virus (HHV-4): new andemerging treatment strategies. Virus Adaptation and Treatment 2010:2 135-145

•Lerner AM, Beqaj SH: A paradigm linking herpesvirusimmediate early gene expression apoptosis and myalgic encephalomyelitis/chronicfatigue syndrome. Virus Adaptation and Treatment 2011:3 19-24

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Patent Information

•A US patent (CFS LLC and The Ohio State University) is underway to be filed, February 2012, describing serum antibody to molecular markers EBV EA(D), EBV dUTPase and EBV DNA polymerase for diagnoses of EBV subset ME/CFS.

•CFS LLC has a US patent application pending entitled Methods for Diagnosis and Treatment of Chronic Fatigue Syndrome. Inventor Lerner, Albert Martin. Agents Barry, Thomas F. et al: Venable LLP, P.O. Box 3485 Washington, DC 20043-9998 (US). This patent differentiates Group A and Group B CFS.

Further information concerning patents owned by CFS LLC can be found in US Pat Nos 5,872,123; 6,258,818; 6,399,622; 6,537,997 and 6,894,056.

© 1998 - 2008 Dr. A. Martin Lerner CFS Treatment Center ; Last revised: February 2011

EIPS® and Energy Index Point Score ® are trademarks of the Dr. A. Martin Lerner CFS Treatment Center. All rights reserved. This document may be copied for use by physicians and patients, but may not be modified, sold, or distributed promotionally in any form without express written permission.

For more information visit: treatmentcenterforcfs.com

Hydrotherapy for ME/CFS - Dr. Cheney's Protocol

The DAR state forest in Goshen, MA - my "swimming hole"

In the 1990s, Dr. Cheney proposed the idea of cool-water hydrotherapy for ME/CFS patients. The idea behind the treatment was that vertical immersion in cool (not cold) water would help down-regulate immune system activation, which Dr. Cheney believed was an integral part of ME/CFS symptoms. 

Allergies, flu-like symptoms, and food sensitivities are all signs of immune activation, as are autoimmune comorbidities (e.g. Hashimoto's disease). Because I had all of these, as well as heat intolerance, I decided to put Dr. Cheney's theories to the test. I immersed myself in cool water (see photo), twice a day for roughly 15 minutes. The water was too cool to simply stand, so I swam very slowly using a modified breaststroke - head above water, body at roughly a 45-degree angle - for about 15 minutes.

The first thing I noticed was that my head cleared. All my cognitive problems disappeared for a few hours after getting out of the lake. My energy levels also improved, as did my stamina.

It turned out that there was more to Dr. Cheney's theory than lymph fluid reversal. Immersion in cool water shunts blood to vital organs - specifically to the heart and brain. (Heat has the reverse effect.) Swimming in cool water for a short period of time helped clear my  head simply because my brain was getting more blood, and, as a consequence, more oxygen.

For those who are interested, I have pasted Dr. Cheney's original hydrotherapy program below. While Dr. Cheney recommended working up to an hour or more, I found that 10-30 minutes was more than sufficient.

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CHRONIC FATIGUE SYNDROME TREATMENT PROGRAM USING HYDROTHERAPY

Introduction

Patients with Chronic Fatigue Syndrome (CFS) have evidence of immune activation. Many of the symptoms associated with CFS may in fact be the result of or indirectly related to an overactive immune response. A substantial reduction in these symptoms may therefore occur with the down-regulation or re-regulation of this overactive immune system.

There are two methods of interest to us which are both inexpensive and have low side effects which can conceivably provoke immune down-regulation in CFS. A low temperature method and perhaps the more powerful pressure gradient method used to accelerate lymphatic flow. These methods could obviously be merged.

Clinicians in Germany have recently used low temperature water baths to treat both Multiple Sclerosis (MS) and Chronic Fatigue Syndrome both of which have evidence of immune activation. It has been observed that Multiple Sclerosis patients worsen when they are overheated by vigorous exercise or after Jacuzzi hot water bathing. MS patients, however, seem to do better after swimming, perhaps because there is much less overheating during this type of exercise.

Several CFS patients treated at The Cheney Clinic using the German cold-water treatment method have reported "windows" or short time periods of improvement following this treatment. As in MS, it has been observed that CFS patients also worsen after being overheated, whether by exercise or by hot water bathing. The two disorders are, of course, immunologically similar in terms of immune activation.

With respect to pressure gradient therapy, there have been two double blind placebo controlled trials documenting at least partial efficacy in CFS of IV gammaglobulin infusion at high dose.

Gammaglobulin is an immune modulator and in addition to being a source of antibodies, possesses a number of immunomodulatory proteins which are known to down-regulate or re-regulate immune system function. 

Tissue lymph fluid bears some resemblance to gammaglobulin as it also contains antibodies and immunomodulatory proteins. The tissue lymph in Chronic Fatigue Syndrome patients is likely to contain immune activation proteins or cytokines in excess. Given evidence in CFS of lymphadenitis and tenderness along lymph node channels, especially in the lower left base of the neck, it is likely that there is increased production of tissue lymph related to their immune activation state.

This excess lymph flow would be expected to back up from the thoracic duct and provoke tenderness in the

Virchow's node area above the left clavicle and extend up into the left middle and posterior cervical node chains and/or into the left axillary (armpit) node chain. In our experience, this is exactly what is seen in most cases of Chronic Fatigue Syndrome. Lymphatic congestion could provoke pain in the left shoulder, left arm and down into the anterior chest. Severe lymphatic congestion would produce tissue edema or fluid retention and perhaps more extensive pain and gastrointestinal complaints, all common in CFS.

Vertical immersion in water creates a significant pressure gradient which can enhance lymphatic flow up the body and torso and into the thoracic duct which lies below the left clavicle The pressure gradient effects would act to autotransfuse tissue lymph back into the blood stream at the level of the left subclavian vein. 

This autotransfusion of excess immunoreactive lymph fluid would likely provoke a down-regulatory immune response which with time could result in a significant improvement in symptoms. Factors which may enhance this lymphatic flow and its effects include water temperature, length of vertical immersion, and the number of days per week in which therapy takes place.

Temperature may be a particularly important variable. Lower temperatures may be better as noted above by the Germans; however, low temperatures may also mitigate against prolonged immersion since as the patient's body cools down, a greater proportion of their energy will be shifted to maintain body temperature, and they then may become more fatigued. On the other hand, higher temperatures accelerate immune activation states and may be counter productive.

It is likely that a temperature somewhere between 80 and 86° is the best compromise between these two issues. It is also felt that length of time per session may be important. At least an hour to an hour and a half per session will likely be required to provoke sufficient lymphatic flow in most patients. The number of sessions per week could also be important and from preliminary studies, it would appear that a minimum of three sessions per week will be necessary.

Factors which may inhibit improvement include lymphatic blockage especially at the Virchow's node area which would be suggested by discomfort in that area following total body immersion. It is also possible that sicker patients may lack sufficient ability to down-regulate against tissue lymph, and, therefore, no significant improvement will be seen. There is also an outside chance that in some patients this therapy could actually exacerbate their condition in the early stages of therapy since the tissue lymph is rich in immune augmenting cytokines.

Finally, it is possible that good hydration will also aid tissue lymph flow, and we would recommend that patients on this protocol drink at least eight glasses of water per day and that sicker patients even consider an infusion of a full liter of IV fluids prior to immersion.

Instructions: Sixteen Week Treatment Protocol

It is important that the pool have water temperatures between 80° and 86°.

Patients will float and occasionally "water walk" primarily in the deep end of the pool and are encouraged to socialize while in the water. Water resistant, head-mounted tape or radio players to listen to audio tapes of books, music or radio can be used to help pass the time. Patients must remain as vertical as possible and submerged to the neck while in the water. The ideal time each patient should stay in the water and the ideal number of sessions per week may vary from individual to individual.

The Cheney Clinic recommends that patients attempt to reach a minimum immersion time of one hour per session for three sessions per week. Longer times per session or more sessions per week may be helpful for some and not for others. Each person will need to determine what is ideal for them. Please note that "water walking" or water exercising is not necessary and can be detrimental in the early phases of treatment. With time, however, water walking may be the ideal exercise for CFS patients. Remember that 30 minutes of water walking is equal to two hours of land walking. CFS patients should be very cautious about overextending in the pool.

Most patients report at first feeling more fatigued or tired after their Hydrotherapy sessions. With time, however, they will typically better tolerate the sessions.

The length of time spent in the water should be increased gradually over the first three weeks starting at 15 minutes per session at a frequency of three times per week. Add 5 to 10 minutes to each successive session over the first three weeks. Never jump ahead to longer times as this has provoked worsening of symptoms in some patients. Session length may need to be abbreviated if you are feeling worse over time and sessions should be omitted on a down-day or if you have a fever above 100 degrees. No session should extend beyond one and one-half hours and a session should be cut short if you become cold or shiver.

Patients will take care to drink at least eight, 8-ounce glasses of water or juice per day. They are particularly encouraged to drink at least twelve ounces of water or non-citrus juice up to but not beyond one hour prior to water immersion. Non-citrus juices include apple, pineapple, papaya and cranberry juices.

Care must be taken to not use hot water showers before or after immersion. This could activate the immune system, especially after immersion. Prior to and following immersion a warm but comfortable shower should be taken. A warm but comfortable then five minutes of cool but comfortable shower method should be used at all other times. No hot water Jacuzzis, saunas, or hot water bathing should be used during this program nor at any other time by CFS patients.

Patients who are cold intolerant or get too cold in the pool should invest in a wet suit. We recommend the O'Neil, full or partial length wet suit as it is relatively easy to get into and out of and can be worn to the pool. Torso thickness should be a three and limb thickness a two. (ie. a 3/2 thickness wet suit). A wet suit can greatly increase the comfort level of longer times in the pool. A wet suit will also increase buoyancy.

Patients who are improving on this therapy must guard against physical, emotional, or cognitive overextension. Patients remain brittle for some time and subject to relapse even as they improve on Hydrotherapy. What you chose to do with your improved functional status may well dictate how successful this program will be for you.

ME/CFS: From Infectious Disease to Autoimmune Disorder

Dr. Kenny De Meirleir spoke at the Whittemore Peterson Institute on January 28, 2013. The following summary of his talk was posted on January 30 on WPI's blog, Wings of Hope. 

Dr. Vincent Lombardi, WPI Research Director, introduced Dr. De Meirleir as one of the world's foremost experts in ME and primary research collaborator on WPI’s current RO1 federal grant. He also stated that Dr. De Meirleir has authored hundreds of publications and several books on ME/CFS and other medical research topics. Dr. Daniel Peterson, who was in the audience, was also recognized for his outstanding contributions to this field of medicine.

Dr. De Meirleir's talk included years of significant research which is very technical and complicated. Therefore, this review is not meant to be a summary of the underlying science but rather a summary of the practical application of this work. However, we will place a recording of this talk on the WPI website: www.wpinstitute.org, as soon as possible for those who are interested in the actual research data.

Dr. De Meirleir presented a comprehensive lecture on the many factors that appear to play a role in the pathophysiology of ME.  In support of his conclusions, he drew information from other well-known researchers in the field including Drs. Chia, Klimas, Peterson, Mella and Fluge, as well as his more recent clinical studies of patients from Belgium and Norway. After the one hour and fifteen minute presentation, interested patients, researchers, doctors, nurses, and medical students were given a chance to ask questions.

Dr. De Meirleir uses a number of diagnostic tests to diagnose his patients’ underlying biological abnormalities and to guide his successful treatment protocols. Biomarkers include abnormally low NK cell number and function, cytokines indicating a shift in the balance of Th1 and Th2 immune responses, up regulation of Th17 immune cells, and abnormal levels of nagalase and elastase activity. He also tests for various active infectious agents including Borrelia, Bartonella, Brucella, mycoplasma, parasites, and various herpes viruses. He stated that environmental and genetic factors contribute to aberrant protein conformation in some patients.  Other diagnostic tests include fecal analysis and tests for levels of LPS or soluble CD14 as an indicator of gut inflammation.

Basic to Dr. De Meirleir’s treatment protocol is a plan that addresses specific dietary restrictions. He reported that many patients are fructose, lactose, casein and/or gluten intolerant. His patients often begin feeling better after eating a diet free of these substances, as they are most likely to cause an inflammatory response. In addition, he includes a fecal microbial analysis to determine whether or not to begin treatment with pulsed antibiotics. Based on the fecal analysis, which indicates whether or not his patients are suffering from a compromised intestinal barrier, he also prescribes specific probiotics, prebiotics such as lactoferrin, and digestive enzymes. When viruses or other pathogens become chronic Dr. De Meirleir prescribes antiviral therapies and/or additional antibiotic treatments.

It is generally accepted knowledge that ME patients have difficulty controlling various herpes viruses and other pathogens, in addition to exhibiting abnormal natural killer cell function. Subsequent searches for immune modulating drugs have included trials of several different products. Gc-MAF is a macrophage stimulating substance that has recently shown great promise.  Dr. De Meirleir highly recommends that patients address any leaky gut issues before beginning treatment with Gc-MAF.  He also mentioned risks that can be associated with this type of treatment.  Risks include a shift to autoimmunity and an immune reconstitution reaction known as IRIS although  none of his patients have developed autoimmune disease as a result of Gc-MAF treatments and less than 20% have experienced IRIS. Dr. De Meirleir routinely monitors his patients for IRIS cytokines after starting them on very low doses of Gc-MAF, as a method of prevention. Other immune supportive therapies include the use of Kutapression/Hepapressin complex (Nexavir), which has been reported to inhibit EBV and HHV-6, and Isoprinosine for those with low serum uric acid levels. Finally, Rituximab, a B-cell depletion immune therapy, has been used successfully in a small trial of patients with ME by oncologists Fluge and Mella. Because of the delayed therapeutic response of two to seven months, the authors of this study remarked that there is a possibility that ME has an autoimmune component. (Note: These two physicians are now looking for collaborative research sites and additional funding to engage in a much larger clinical trial due to their 67% rate of success.)

Dr. De Meirleir concluded his talk with a detailed slide describing the various pathways that are disrupted in ME and several other autoimmune diseases. He spoke about a continuum of autoimmune diseases including ME, lupus, RA, type 1 diabetes, and remitting MS that involve a dysregulation of two important immunological pathways, 2’-5’OA synthetase and Th1/Th2 immunity.

It was evident from his lecture that the key to Dr. De Meirleir’s success with patients is his recognition of the serious infectious and immunological issues facing those with ME. His research provides strong evidence for the support of biological testing and treatment.

WPI is thankful to Dr. De Meirleir for his outstanding commitment to this patient population. We feel fortunate to be able to provide his lecture as part of our mission to support outreach and education. We look forward to sharing more good news with you in the future.

Dr. Derek Enlander's Treatment Protocol for CFS/ME

Dr. Derek Enlander is a native Irishman from Belfast. He came to New York as Assistant Professor of Medicine at Columbia University and then became Associate Director of Nuclear Medicine at New York University. Dr. Enlander is on the faculty of Mount Sinai Medical School and is an attending physician at Mount Sinai Medical Center in New York.

Dr. Enlander's protocol is based on treating the immune system dysfunction that underlies CFS/ME. He has an active research program, including Ampligen and GcMAF, in which his patients are invited to participate. Dr. Enlander is the founder of the ME/CFS Center, an international collaboration which includes virologist Illa Singh, geneticist Eric Schadt, immunologist Dr. Miriam Merad, Dr. Kenny De Meirleir and Dr. David Bell. (Sadly, videos of the 2011 Mount Sinai ME/CFS conference are no longer available.)

The following are current treatments used by Dr. Enlander (taken from his website). (Please go to Dr. Enlander's website for current treatments.)

Hepapressin Injection: Hepapressin is an amino acid complex similar to Kutapressin, derived from Argentinian bovine liver. Like Kutapressin, it is an immune system adjuvant. As Hepapressin on its own is rarely effective, Dr. Enlander combines the injection with his own specialized formula to produce a more efficient complex.

Immune Resist is an amino acid food additive. It is an oral capsule taken once daily. It is thought to be involved in the immune system and may diminish fatigue and "brain fog," and assist in concentration and short-term memory.

IMMUNOPlus: Immunoplus is given as an adjunct to Immune Resist. It contains folinic acid, along with other amino acids and other components in the methylation cycle. Dr. Enlander believes that the methylation cycle is part of the CFS/ ME dysfunction. 

Catapult contains phosphatidyl serine and cat’s claw. It is a non-prescription OTC supplement used to diminish "brain fog." Dr. Enlander reports quite good results with it. 

Neurontin: Neurontin is a prescription drug used as an anti-epileptic in grand mal seizures. In CFS and fibromyalgia the abnormal impulses that come from the brain are thought to be suppressed by Neurontin, allowing muscle fibers to be less fatigued. The daily dose can be up to 2400 mg per day.

Experimental Treatments

Low Dose Naltrexone (LDN): Opiate receptors are activated by naltrexone, which in low dose produces a cytokine reaction. This is thought to be helpful in CFS. Dr. Enlander states that it is too early to determine the effects.

LECTROLYTE or RECUP (a Spanish Electrolyte mixture) has been successful in fortifying muscles. LECTROLYTE may also reduce muscle pain. It contains 450 mg sodium, 125 mg potassium, 15 mg each of calcium and magnesium. LECTROLYTE does not contain sucrose or fructose (RECUP does contain these sugars).

Valcyte: Valcyte is a prescription antiviral medicine that Dr. Montoya at Stanford University has shown to be effective against the HHV-6 virus. Dr. Enlander collaborated in a study of Valcyte under the auspices of the HHV-6 Foundation. Patients interested in this treatment are encouraged to contact Dr. Enlander's office.

Ampligen: Dr. Enlander is cooperating with Hemispherx Corporation in a study of Ampligen in the treatment of Chronic Fatigue Syndrome.

GcMAF: GcMAF is a naturally occurring substance in the human body which destroys pathogens by activating macrophages. Several CFS physicians, including Dr. Cheney, Dr. De Meirleir, and Dr. Elson (Northampton, MA), have begun using GcMAF for patients who test high in nagalase, the enzyme that destroys naturally occurring GcMAF in the body.

EECP Treatment: EECP (enhanced external counter pulsation) therapy is an outpatient treatment used to improve blood circulation and increase cardiac output. It is normally used for angina and heart failure. In ME/CFS the treatment sessions are 30-45 minutes and are given once a week. During the treatment, the patient lies on a comfortable treatment table with large blood pressure-like cuffs wrapped around the legs and buttocks. These cuffs inflate and deflate continuously at specific times between heartbeats, a continuous electrocardiogram (EKG) set the timing so the cuffs inflate while the heart is at rest, in diastole, when it normally gets its supply of blood and oxygen. The cuffs deflate at the end of that rest period, just before the next heartbeat, systole. When timed correctly, this will decrease the afterload that the heart has to pump against, and increase the preload that fills the heart, increasing the cardiac output.

CONTACT:

Derek Enlander, M.D.
860 5th Avenue, Suite 1C
New York, NY 10065
Phone: (212) 794-2000
Fax: (212) 327-2125
Email: mecfsoffice@enlander.com
Website: http://www.enlander.com/

Dr. Enlander accepts Medicare (not HMO), Medicaid (NOT) managed care, GHI-HealthNet- HMO – POS, PHCS, United Health, Cigna, JJ Newman, Oxford freedom Plan..