About Us
We would like to welcome you to the web-site of the Campaign for an Irish ME clinic in Ireland. There are approximately 45,000 people suffering from ME in the Republic of Ireland today (using the 0.42% - 1% figure in the International Consensus Criteria, 2011). Many of these people are severely ill and bedridden, and many are confined to wheelchairs or housebound. Many are undiagnosed due to lack of accurate medical diagnostic tests and lack of knowledge about the illness. The objective of our organisation is to get private investors, big private equity funds or the Irish government to build an ME Clinic in Ireland, which would provide state of the art diagnosis and treatments using best international practises. We have extensively researched doctors, specialists and clinics who have successfully treated ME in other countries and researched what is best international practise for treating the illness. These scientific and medical findings and recommendations  would be the starting point for designing the structure and operation of an ME Clinic in Ireland.

The need for an Irish ME clinic is based on research conducted by the Irish ME Trust around 2003 which found that over 80% of GP's would desire this as it would provide a place to send patients to where they could avail of medical specialists with expertise in the illness (http://www.imet.ie/imet_website/the_irish_position/a_clinic_for_ireland.html). The complexity of ME, CFS, Fibromyalgia and Chronic Lyme disease requires specialist medical doctors with a high level of training, experience and knowledge. The experience in other countries, especially from private clinics, shows that specialist ME (CFS) clinics, Fibromyalgia clinics and Chronic Lyme disease clinics are the most effective and cost efficient means of treating these complex diseases

What is ME ?
M.E. stands for Myalgic Encephalomyelitis which is a Latin name meaning inflammation of the brain, spinal cord and muscles. Myalgic Encephalomyelitis or ME was first used to define the illness by Dr. Donald Acheson in the Lancet medical journal in 1955 and has been used ever since - Outbreak at the Royal Free. E.D Acheson. The Lancet, Volume 266, Issue 6886, Pages 394 - 395, 20 August 1955. ME is the correct scientific and medical name for the illness. The World Health Organisation (WHO) classification code for ME is G93.3, World Health Organisation - Classification . This is universally accepted by governments, medical associations and doctors worldwide. This puts ME in the same class as other neurological illnesses such as Multiple Sclerosis, Parkinsons, ALS, Epilepsy. The research, much of it listed on this web site, verifies that it is a neurological illness with immune deficiencies, endocrine abnormalities, mitochondria dysfunctions, and chronic infections in many cases

ME type epidemics prior to 1955, are listed on the following link ME Epidemics . They date back to 1917, but there is a general medical and scientific consensus that the illness itself is far older, as epidemics in the past would would not have been identified and defined due to primitive medical knowledge and techniques, and totally inadequate medical technologies. Past epidemics would have used several terms to define the illness, examples being ‘Epidemic  Neuromyasthenia’, 'Atypical Poliomyelitis’, 'Iceland disease', ‘Encephalitis’,  'Encephalitis lethargica', Neurasthenia', ‘Akureyri Disease’,  ‘Poliomyelitis-like epidemic neuromyasthenia’, 'Diencephalitis',  ‘Abortive Poliomyelitis’. These are mentioned in the following research papers:

- A new Clinical Entity ? . Bjorn Sigurdsson. The Lancet, 1956
- The Clinical Syndrome Variously Called Benign Myalgic Encephalomyelitis, Iceland Disease and Epidemic Neuromyasthenia. Dr. Acheson, American Journal of Medicine, 1959.
- Parish JG (1978), Early outbreaks of 'epidemic neuromyasthenia', Postgraduate Medical Journal, Nov;54(637):711-7, PMID: 370810
- Sigurdsson B, Sigurjonsson J, Sigurdsson JHJ, Thorkelsson J, Gudmundsson KR. A disease epidemic in Iceland simulating Poliomyelitis. Am J Hyg 1950; 52: 222-238.
- CLINICAL FINDINGS SIX YEARS AFTER OUTBREAK OF AKUREYRI DISEASE. Bjornn Sigurdsson. The Lancet Volume 267, Issue 6926, 26 May 1956, Pages 766-767
The Clinical and Scientific Basis of Myalgic Encephalomyelitis--Chronic Fatigue Syndrome by Byron Hyde, by Dr. Jay Goldstein, P. Levine, Nightingale Research Foundation.

In the USA, the name M.E. was used from the 1950's to the 1980's. In 1985, there was an ME type epidemic in the Lake Tahoe area in the USA. This ME type illness was given the name 'Chronic Fatigue Syndrome (CFS)' by the CDC in 1988. Though at the CDC meeting, there were sharp divisions between older, experienced medical doctors who wanted to use the existing term 'ME' to name and describle the illness, and a NIH administrator called Stephen Straus who wanted to invent a new name for the illness calling it 'Chronic Fatigue Syndrome'. Straus succeeded in giving the illness a new name, which proved to be disastrous for both patients and doctors / scientific researchers. The new name has proved very insultng to patients and very ambiguous, vague, and confusing for medical doctors and scientific researchers. This is discussed in more detail in sections below and includes, facts, letters and correspondence.

Central to this new, ineffective and insulting name 'Chronic Fatigue Syndrome' (CFS) are the Lake Tahoe medical and scientific findings which point to chronic immune system dysfunctions, chronic viral infection(s), chronic inflammation, muscular abnormalities, exertion intolerance, and some neurological and endocrine dysfunctions, all of which are found in ME epidemics. The facts are indisputable. Calling ME by another name has confused and divided medical opinion and scientific opinion. Would one call Diabetes "Chronic Thirst Syndrome" or call Cancer "Chronic Weakness and Pain syndrome" or call Alzheimers disease "Chronic Forgetting Syndrome" or call Parkinsons disease "Chronic Tremor Syndrome" or call Anemia "Chronic Tiredness Syndrome" ?? The answer would be no as they are insulting, abusive and tell one nothing about the illness. Then why did Mr. Straus use an insulting and abusive term such as "Chronic Fatigue Syndrome" to describe an ME type illness, an ME epdemic?

There is evidence that Mr. Straus (NIH) acted maliciously to make the illness "evaporate" and disappear and become a non illness - click here to view letter exchanged between Dr. Straus and Dr. Fukuda shortly after the Fukuda definition was approved in 1994. He deliberately worked with others to omit the scientific and medical evidence, give the illness a bad name and a poor quality definition, belittle and denigrate it, deprive it of legitmacy and of research funding, and make the illness disappear. These actions contributed to the deaths of tens of thousands of patients. This was serious medical misconduct. According to Dr. Byron Hyde and other highly distinguished medical doctors and scientific researchers, the Lake Tahoe outbreak was a classic ME outbreak, and the scientific findings have validated and corroborated their beliefs so far. In 2015, the prestigious Institute of Medicine and the American National Academy of Science published their medical and scientific findings about ME in a book "Beyond ME". This was the result of 2 years of research, including a review of 2,700 scientific research papers and expert testimonies by medical doctors and scientists by a 15 strong medical committee. They renamed the illness Systemic Exertion Intolerance Disease (SEID), and stated that: "the term 'chronic fatigue syndrome' can result in stigmatization and trivialization and should no longer be used as the name of this illness."

After 1955, Dr. Acheson's paper which named and described the ME illness, was followed by an article in the Lancet by Sigurdsson describing the illness and it's history A new Clinical Entity ? in 1956. In that same year, a paper by Dr. Melvin Ramsay appeared in the Lancet Encephalomyelitis simulating Poliomyelitis . Dr. Melvin Ramsay was a consultant physician at the Infectious Diseases Department of the Royal Free Hospital, and he also served as advisor to the Ministry of Health in matters concerning smallpox. He was actively involved in treating ME patients during the Royal Free Hospital outbreak. He went on to become a leading global expert in ME, spending 35 years diagnosing, treating and researching ME, and other diseases. There was another paper by Dr. Acheson in the Lancet in 1957 Benign myalgic encephalomyelitis followed by an article in the British Medical Journal titled 'Epidemic Myalgic Encephalomyelitis' in 1957. The ME outbreak at the Royal Free Hospital in Britain continued to interest doctors and researchers as evidenced by the paper An Outbreak of Encephalomyelitis in the Royal Free Hospital Group, London, in 1955 by THE MEDICAL STAFF OF THE ROYAL FREEHOSPITAL in British Medical Journal in 1957. And another paper that year Epidemiological aspects of an outbreak of encephalomyelitis at the Royal Free Hospital, London, in the summer of 1955

In 1957, a paper by an American, Dr. Shelokov , 'Epidemic Neuromyasthenia. An outbreak of poliomyelitis-like illness in student nurses' published in the New England Journal of Medicine provided details of a typical ME outbreak, which was quite new to medical science in America. That year a paper was published in the New England Journal of Medicine about the Punta Gorda outbreak. Another paper in 1958 shed more light on the illness - Benign myalgic encephalomyelitis. Galpine, J.F. Brit. J. Clin. Practice, 12: 186, 1958. This was followed by another more detailed paper by Dr. Acheson in the American Journal of Medicine in 1959, The Clinical Syndrome Variously Called Benign Myalgic Encephalomyelitis, Iceland Disease and Epidemic Neuromyasthenia.n 1959 a paper appeared in the New England Journal of Medicine titled 'Epidemic Neuromyasthenia — Clinical Syndrome?' by Dr. Donald Henderson and Dr. Shelokov and this gave an an American perspective on the disease, ME. In 1955, Pellew and Miles (1955) in Australia reported that the infectious agent in ME patients was transferred to healthy monkeys and they died within a short time. Autopsies showed damage to nerve cells and blood vessels. A medical thesis by Dr. A.L. Wallis in Edinburgh University, 1957 shed some light on the outbreak of ME in Cumberland in the 1950's. An autopsy of a dead patient showed damage to nerve cells and blood vessels. The common consensus among doctors and researchers during the 1950's was that a virus was involved. By 1960, 'Myalgic Encephalomyelitis' (ME) was formally accepted and recognised by medical authorities worldwide, and in 1962 it began appearing in medical text books in University. Dr. Donald Acheson was convinced the illness involved a chronic infection with neurological, muscular and immunological effects and dysfunctions. Dr. Acheson later became the Chief Medical Officer in Britain and was a highly respected medical doctor and researcher.

There were further research papers and reviews produced by other leading medical doctors and researchers including Dr. Melvin Ramsay, Dr. E. O'Sullivan, Dr. Richardson, Dr. Galpin, Dr. Deisher, Dr. Parish, Dr. Shelokov, Dr. Henderson, Dr. Sigurdsson, Dr. Poskanzer, Dr. Gsell, Dr. Hill, Dr. Dowsett, Dr. Behan and others in medical and scientific journals throughout the 1950's, 1960's, 1970's and 1980's, see History of ME presented by Lisa Petrison to the CFSAC in 2014
. They all concluded that an infectious disease, neurological dysfunctions, musco-skeletal dysfunctions, exhausation, mitochondria abnormalities, and severe inflammation were involved in the illness.

It's neurological aspects were considered important by the medical community, and ME was formally classified by the World Health Organisation as a neurological disorder in the International Classification of Diseases (ICD) in 1969 (ICD-8: Vol I: code 323, page 158; Vol II (Code Index) page 173). 

Dr. Melvin Ramsay, a British medical doctor was a leading global authority on ME from 1955 to 1990, and his work was cited and used by doctors around the world. He believed that there was an infectious cause which led to neurological, endocrine, mitochondria and muscular abnormalities. His research paper 'Epidemic neuromyasthenia' 1955-1978'. Postgrad Med J. 1978 Nov;54(637):718-21. PMID: 746017, was a major contribution to medicine, and provided important insights into the illness in Britain over 2 decades. His classic book about ME, detailing its naming, definition and it's progression through the 1950's, 1960's and 1970's is Myalgic Encephalomyelitis and Post Viral Fatigue States: the Saga of the Royal Free Disease by Dr Melvin Ramsay. Dr. Ramsay knew and collaborated with Dr. Acheson and Dr. Richardson, throughout this period and their medical and scientific insights were very valuable and continue to have relevance today. Dr. Ramsay was the first person to create a formal definition and diagnostic criteria for the illness in 1986, which was used by doctors and researchers in Europe - Ramsey ME Definition 1986, 1988

Dr. John Richardson, a medical doctor based in Newcastle in England treated ME patients from many parts of Britain for over 40 years. He developed an expertise in diagnosing the illness, and became one of the world's foremost experts in ME. He even used autopsy results from dead patients to investigate the illness. He found that Enteroviruses and toxins played a major role in ME, and that this led to immune dysfunction, neurological abnormalities, endocrine dysfunction, and over time to increased risk of cardiac failure, cancers, carcinomas, and other organ failure. He wrote a book about his medical experiences called Enteroviral and Toxin Mediated Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. This book is a classic medical book on the illness, and provides an excellent introduction to ME.

Dr. Erich Ryll a US doctor based in California studied ME patients from 1975 to 1994. He concluded that it involved infectious vasculitis, extreme inflammation, severe exhausation, and that an infectious disease was involved. Vasculitis involving the skin was recorded during ME outbreaks in Cumberland, Durham and North West London in Britian in 1955. This has been confirmed by later studies showing significant vascular abnormalities and damage to veins in ME patients.

WHO Classification
ME is the correct scientific and medical name for the illness. The World Health Organisation (WHO) classification code for ME is G93.3, World Health Organisation - Classification . This is universally accepted by governments, medical associations and doctors worldwide. This puts ME in the same class as other neurological illnesses such as Multiple Sclerosis, Parkinsons, ALS, Epilepsy. The research verifies that it is a neurological illness with immune deficiencies, endocrine abnormalities, mitochondria dysfunctions, and chronic infections in most cases.

Medical Diagnostic Protocols and Treatment Protocols using Best International Practices
ME is a chronic physical illness, which is multi-factorial, involving immune system dysfunctions, neurological dysfunctions and abnormalities, chronic infections of the nervous system, brain, muscles, glands and intestines in subgroups of patients, HPA axis and endocrine dysfunctions, mitochondria abnormalities and dysfunctions and cardiac and vascular system abnormalities. CFS is an ME type illness first defined during the Lake Tahoe Epidemic in the 1980's in the USA, and CFS and ME share many similarities. 'Lake Tahoe illness' would be a more appropriate term than CFS, as it is associated with that epidemic. Some doctors and researchers believe that ME and CFS are the same illness, and they cite previous names for ME such as ‘Epidemic  Neuromyasthenia’, 'Atypical Poliomyelitis’, 'Iceland disease', ‘Encephalitis’,  'Encephalitis lethargica', ‘Akureyri Disease’,  ‘Poliomyelitis-like epidemic neuromyasthenia’, 'Diencephalitis',  ‘Abortive Poliomyelitis’. Fibromyalgia is common in both ME and CFS patients, and has it's own biological markers. There is international agreement between experienced doctors, scientific researchers, medical authorities and governments in relation to what constitutes ME and CFS and Fibromyalgia and the diagnostic and treatment guidelines.

ME Diagnostics

  1. Rule out Other Illness with very similar symptoms to ME. Some of these will require use of newer, more advanced diagnostic technologies

  2. World Health Organisation - Classification of ME. This is universally accepted by governments, medical associations and doctors worldwide.

  3. Myalgic encephalomyelitis: International Consensus Criteria, 2011.This supercedes 'Myalgic Encephalomyelitis / Chronic Fatigue Syndrome: Clinical Working Case Definition, Diagnostic and Treatment Protocols (2003)' listed below.

    ME Primer for Healthcare Professionals: based on Myalgic encephalomyelitis: International Consensus Criteria, 2012

  4. Myalgic Encephalomyelitis / Chronic Fatigue Syndrome: Clinical Working Case Definition, Diagnostic and Treatment Protocols, 2003

    For Medical Doctors - Myalgic Encephalomyelitis / Chronic Fatigue Syndrome: Diagnostic and Treatment Protocols, 2003

  5. US National Academies of Science, Institute of Medicine report, 2015: "Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness"

  6. The Nightingale Definition of Myalgic Encephalomyelitis (M.E.), 2011

  7. Ramsey ME Definition 1986, 1988

Fibromyalgia Diagnostics

  1. Fibromyalgia Diagnostics


The Research Findings

Listing of Research findings and papers worldwide and categorisation of biological abnormalities and dysfunctions and infections found in ME

  1. Immune system dysfunction and abnormalities
  2. Genetic markers
  3. Severely Damaged Mitochondria and Defective Krebs cycle and ATP production
  4. Viral infections
  5. Mycoplasma infections
  6. Serious Bacteria infections
  7. Molds & Mycotoxins & Immune Dysfunctions
  8. Micro RNA (miRNA) profiles
  9. Cryptostrongylus Pulmoni infection
  10. Vaccines and ME/CFS
  11. Increased risk of Cancer
  12. Environmental Toxins, Heavy Metals, Organophosphates
  13. Orthostatic intolerance & Postural orthostatic tachycardia syndrome (POTS) & Body fluid abnormalities
  14. Serious Brain and nervous system abnormalities
  15. Spinal Fluids & Proteomic Markers
  16. Cognitive Dysfunctions & 'Brain Fog'
  17. Effects of Exercise, GET and CBT
  18. Muscle abnormalities
  19. Abnormal HPA axis (Hypothalmus Pituary Adrenal axis) & Abnormal glandular functions
  20. Intestinal Abnormalities and Microbiome
  21. Cardiac and Vascular and Blood vessel problems. Increased risk of heart attack
  22. Idiopathic CD4+ T lymphocytopenia
  23. Methylation cycle blocks and glutathione deficiency
  24. Increased oxidative stress
  25. Channelopathy & Disturbance in the way certain ions (mainly sodium and potassium salts) are transported in and out of cells across the cell membranes
  26. Sleep abnormalities
  27. Ciguatera and ME
  28. Telomere shortening
  29. Abnormal red blood cell structure
  30. Abnormal Sedimentation rates
  31. Inability to metabolise glucose and sugar
  32. Defects in Lymphatic Drainage
  33. Lowered oxygen consumption in ME patients
  34. Substance P is elevated in ME patients
  35. Abnormal Plasma RNA's
  36. Abnormal Urinary metabolites
  37. The presence of crimson crescents in the mouth
  38. Beta 2 microglobulin levels as a measure of the severity of the condition
  39. Abnormal levels of serum Chromogranin-A. Evidence of Celiac disease in some ME patients
  40. Skin rashes, acne and allergies worsen after the onset of ME
  41. Clonal Excess Abnormality
  42. Other Serious Abnormalities
  43. Sub-groups within ME

The following paper by the organisation Paradigm Change details many of the biological abnormalities, dysfunctions and infections found in ME and CFS patients and research papers to support this.
ME/CFS and Medical Abnormalities - Medical Research paper.

The Dubbo Studies which were published in leading medical journals verify much of the above, and point to genetic factors, environmental factors and a post-infectious dysfunctional immune system as being the key factors in ME / CFS.

Post-infective and chronic fatigue syndromes precipitated by viral and non-viral pathogens: prospective cohort study. Hickie I, Davenport T, Wakefield D, Vollmer-Conna U, Cameron B, Vernon SD, Reeves WC, Lloyd A; Dubbo Infection Outcomes Study Group. BMJ. 2006 Sep 16;333(7568):575. Epub 2006 Sep 1.

Cytokine polymorphisms have a synergistic effect on severity of the acute sickness response to infection. Vollmer-Conna U, Piraino BF, Cameron B, Davenport T, Hickie I, Wakefield D, Lloyd AR; Dubbo Infection Outcomes Study Group. Clin Infect Dis. 2008 Dec 1;47(11):1418-25. doi: 10.1086/592967.

Summary
The scientific research, much of it catalogued above and in the Scientific Evidence Section, shows that ME is Multi-Factor illness, a chronic disabling physical illness, which involves multiple biological dysfunctions and abnormalities.
According to gene studies and other biological studies, there are at least 5 subgroups in ME / CFS. Many patients also have co-existing illnesses. We are dealing with a high level of biological complexity here. The research strongly suggests the illness involves the following

Primary biological dysfunction and abnormality
(1)
ATP, mitochondria & krebs cycle dysfunctions
The research and clinical work of Dr. Sarah Myhill, Dr. Behan and Dr. Paul Cheney and other doctors and researchers have consistently found this biological abnormality. Deficient ATP produced and deficient recycling of ATP. A rapid shift to anerobic metabolism, build up of lactic acid, purines, muscle pains etc. during and after exercise, and post-exercise malaise commonly found in ME patients. Oxidative & Nitrosative stress damage to inner & outer membranes of mitochondria, cristae, proteins, and DNA of mitochondria. Krebs cycle blocks. Redox failure. Ion channel interruption & dysfunctions affecting Ca. Mg. and K levels.  Deficient  Electron Transport Chain.  Impaired ATP production and Oxidative Phosphorylation. Impaired Translocator protein activity. Acceleration of AMP & glycolysis. This may be due to chronic infections, a chronically activated inflammatory immune system, hypoxia or lack of oxygen in cells, toxins and the high levels of oxidative and nitrosative stress in the illness. Mitochondria dysfunction is the most important factor as the mitochondria and krebs cycle produces ATP, which is fuel or energy for the immune system, the nervous system, the brain, the muscles, the heart, the glands, and all the organs. Any significant deficiency in ATP will cause a slow down in the activity of these organs and the body, and more serious deficiencies can cause extreme tiredness most or all of the time. This may explain Cardiac dysfunctions in ME as this can be related to mitochondria dysfunctions, chronic infections and inflammatory damage over time.

Secondary biological dysfunctions and abnormalities
(1) Immune system dysfunctions and deficiencies caused by or accompanied by viral / mycoplasma / pathogen infection (active and latent) and/or toxins. Overactive 2'-5' oligosynthetase pathway, defects in the 2-5a synthetase / RnaseL anti-viral pathway & PKR pathway with effects on immune system function and important ion channels. In the case of the 2-5a synthetase / RnaseL anti-viral pathway, it is believed that human leukocyte elastase and/or calpain cleaves the 80 kDa form of RnaseL into 37 kDa RnaseL, cleaves STAT1-alpha protein and p53 protein and Actin, bringing about deficiencies in these proteins. These proteins are essential for normal immune system function, and their depletion and abscence leads to serious and continuing immune system dysfunction. These abnormalities strongly indicate an immune system which is being activated by chronic viral infection, and the immune system is becoming depleted or defective over time.
There is an accompanying increase in NF-Kb levels and activity which is pro-inflammatory. Low numbers of NK cells and reduced NK cell function and cytotoxicity. The Rituximab studies show that B cell abnormalities, including excessive levels of defective B cells are a major factor and may perpetuate the illness. This may be the result of a past infection or chronic infection of B cells. Chronic immune system activation with dominance of pro-inflammatory cytokines. T cell abnormalities, including depleted Suppressor cells, CD8 and T reg cell abnormalities and an abnormal CD4/CD8 ratio. Retrovirus infections have been found in ME patients, and these infections can deplete T cell suppressor cells and other T cell subsets. Interferon poisoning in some subgroups of patients, and this is is also linked to viral infections. The overactive immune system is progressing to autoimmunity in some cases, there are HLA abnormalities and other evidence of autoimmunity in many patients. VDR abnormalities which weaken immunity, and increase susceptibility to chronic infection and autoimmune risk (Dr. Marshall, Marshall Protocol). Gastrointestinal abnormalities which contribute to immune system dysfunctions. The immune system has a high demand for ATP in this illness, while ATP is being depleted through mitochondria destruction or degradation.
(2) the evidence from prior ME epidemics show that infections play a role in most ME patients. Top ME doctors A. Gilliam, Melvin Ramsay, Elizabeth Dowsett, John Richardson of Newcastle-upon-Tyne, W.H. Lyle, Elizabeth Bell, James Mowbray of St Mary’s, Peter Behan and Byron Hyde all believed that the majority of primary M.E. patients fell ill following exposure to an Enterovirus. Dr. John Richardson, a medical doctor based in Newcastle in England treated ME patients from many parts of Britain for over 40 years. He developed an expertise in diagnosing the illness, and became one of the world's foremost experts in ME. He even used autopsy results from dead patients to investigate the illness. He found that Enteroviruses and toxins played a major role in ME, and that this led to immune dysfunction, neurological abnormalities, endocrine dysfunction, and over time to increased risk of cardiac failure, cancers, carcinomas, and other organ failure. He wrote a book about his medical experiences called Enteroviral and Toxin Mediated Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. This book is a classic medical book on the illness, and provides an excellent introduction to ME. Historically, Enterovirus infections mainly target the nervous system, brain, muscles and intestines, all of which abnormal in ME patients.
In subgroups, there is evidence of Retrovirus infection and Herpes infections and changes to cell structures and to T cell subsets. There is evidence for continuing viral, mycoplasma, bacteria and other pathogen infections (both active and latent, including partially latent) of the nervous system, nerve junctions, brain, immune system cells, intestines, joints, muscles, and other body organs. These infections may be causative, opportunistic or a co-factor in the illness. There are high levels of oxidative and nitrosative stress and inflammation, and cellular destruction, arising from chronic immune system activation, infections, immune system and cellular dysfunctions, and toxins.
(3) dysfunctions of the central nervous system, the brain and the autonomic nervous system, and involves significant chronic inflammation, lesions, reductions in grey and white matter, brain hypoperfusion, increased ventricular lactate, spinal fluid abnormalities, autonomic dysfunctions and other abnormalities. This adversely affects many other body functions.
(4)
Dr. Paul Cheney has found toxic build up in the body in many patients. Flow reversal in the liver and the brain. Chronic Cerbral Spinal Venous Insufficiency (CCSVI). Chronic He patic Venous Insufficiency (CHVI). Cardiac Dysfunction. This reversal leads to auto-intoxication and a build up of toxins and toxin related damage to cells, tissues, organs, glands, etc.. (Dr. Paul Cheney)
(5) methylation cycle blocks and glutathione deficiency. The methylation cycle is important and produces many substrates and co-factors for other body organs and processes, including the mitochondria. Deficient glutathione increases oxidative and nitrosative stress and this contributes to mitochondria abnormalities and dysfunctions.
(6) HPA axis dysfunctions, in particular hypothalmus gland, adrenal gland and thyroid gland dysfunctions and abnormal hormone output, which adversely affects hormones, sleep and immune function.

All of these 7 factors are the core of the illness, the perpetuating factors over time. Subgroups will contain most of the 7 factors mentioned above. There are slight differences between patient groups which are due to subgroups, genetic differences, different environment exposures and toxins, different infectious agents, different microbiome and metagenome status, and different diet and lifestyles. These abnormalities and dysfunctions have a domino effect on other cellular functions and body functions leading on to several other dysfunctions, and to severe illness.

The immune system dysfunctions and abnormalities in ME patients makes them more susceptible to various infections. The acquired infection(s) will depend on one's geographical location and exposures, and one's genetic status and immune system status. Some of the following pathogens have been consistently found in ME patients:

Viruses include: Reactivated (latent) EBV virus, particularly in nervous system, glands and organs, HHV6a virus, Herpes family viruses 1-8, Parvovirus B-19, CMV, Coxsackie viruses, Enteroviruses, Ross river virus, Q fever virus, Stealth virus, JHK virus,  Parainfluenza Virus-5 (PIV-5), Paramyxovirus and measles viruses of the  Paramyxoviridae family, Cryptovirus, Borna virus, HTLV family viruses, HGRV virus in spinal fluids, nerve tissues, blood, brain, intestines, and muscles. Retroviruses are important, as Retrovirus sequences were found in 85% of ME cases, and Anellovirus found in 75% of ME cases in research conducted by Dr. Hornig and Dr. Lipkin in Columbia University in September 2013. Most of these viruses listed here would include chronic, low level, sub-acute infections which inflict damage and immune activation, but which may not show up in standard or outdated tests.
Reactivated latent viruses include HERV-K18, Varicella-Zoster virus, Herpes family viruses 1-8, measles viruses of the  Paramyxoviridae family. Some viral infections can reactivate latent viruses and undermine immune system functions.

Mycoplasma: M. fermentans, M. penumoniae, M. hominis, M. penetrans, M. pirum,  M. incognito. in intestines, spinal fluids, blood, brain, nerve tissues, muscles. These mycoplasmas would include chronic, low level, sub-acute infections which inflict damage and immune activation, but which may not show up in standard or outdated tests.
Bacteria: Chronic Lyme disease, Ehrlichia, Bartonella, Brucella, Rickettsia, Chlamydia pneumonia, Staphylococcus spp. (live blood analysis), and Bacteria, including Microbiota of bacteria which include L-form, biofilm, and intracellular bacterial forms in spinal fluids, intestines, blood, brain, nerve tissues, muscles. Intestinal overgrowth of Gram positive D/L lactate-producing bacteria which are known to produce H2S (hydrogen sulfide) in the presence of certain heavy metals as a survival defense mechanism (Dr. Kenny De Meirleir). These bacteria would include chronic, low level, sub-acute infections which inflict damage and immune activation, but which may not show up in standard or outdated tests.
Parasite: Cryptostrongylus pulmoni (rare cases), Babesia, Candida, Giardia lamblia, Aspergillus Niger
Molds, Bacteria and Mycotoxins in water damaged buildings: Stachybotrys family of molds, Cladosporium, Penicillium, Alternaria, Aspergillus, mycobacteria, Actinomycetes, Lipopolysaccharides (LPS), Microbial Volatile Organic Compounds (VOCs), Hemolysins. These can cause chronic inflammatory immune response and immune dysfunction over time.

These infections may be causative, opportunistic or a co-factor in the illness.


What is ME and CFS ? Multiple Paths leading into ME and CFS

Causes of Heterogenity, Excessive Subgroups & Phenotypes and inability to find a Universal Biomarker, and the Conflicting Test Results and Treatment Outcomes


Response of some Governments

The Norwegian government's web site at
http://www.helsedirektoratet.no/helse-og-omsorgstjenester/cfs-me/diagnose/Sider/default.aspx
recognises these facts and has recently included the
Myalgic Encephalomyelitis / Chronic Fatigue Syndrome: Clinical Working Case Definition, Diagnostic and Treatment Protocols, 2003 and For Medical Doctors - Myalgic Encephalomyelitis / Chronic Fatigue Syndrome: Diagnostic and Treatment Protocols, 2003 and
A Pediatric Case Definition for Myalgic Encephalomyelitis and Chronic Fatigue Syndrome. Jason LA, et al. (2006) on it's web site and now recommends that doctors and specialists use these diagnostic criteria.

In 2011, the Norwegian Government apologised to ME patients and their families in Norway for neglecting them, and offering ineffective, useless psychiatric and psychological treatments for many years, which left them sick and in limbo. The government announced a change in direction towards biological based diagnostics and treatments and support for biological research such as the Rituximab trials in Norway.
Norway's Directorate of Health Apologises for Treatment of ME Patients


In 2001, Health Canada appointed an international panel of experts in this emerging field of medicine, ME / CFS, to establish a clinical working-case definition, diagnostic guidelines, and treatment procedures. The panel released a set of guidelines in 2003 and their choice of name to describe the condition was both "myalgic encephalomyelitis" and "chronic fatigue syndrome" – with acronyms shortening it down to a manageable size: ME/CFS. This document was legally commissioned and approved by Health Canada. This is a legally enforceable document in relation to patient's rights. It can be enforced through a Canadian court. Many medical doctors now use the Canadian Consensus criteria (2003) to diagnose and treat patients in Canada. See documents below
Myalgic Encephalomyelitis / Chronic Fatigue Syndrome: Clinical Working Case Definition, Diagnostic and Treatment Protocols, 2003
and For Medical Doctors - Myalgic Encephalomyelitis / Chronic Fatigue Syndrome: Diagnostic and Treatment Protocols, 2003 for doctors and specialists in Canada.

The Australian government also recommends use of the Canadia Consensus criteria (2003). This is outlined in the following Australian government web site http://sacfs.asn.au/download/guidelines.pdf

In Japan the Japanese Ministry of Health commissioned and approved a new definition in 2004 called 'Childhood Chronic Fatigue Syndrome', this detailed several immunological, neurological, sleep disorders,. endocrine, infectious factors in the illness.
Childhood chronic fatigue syndrome. Miike T. Nihon Rinsho. 2007 Jun;65(6):1099-104.

In 2008, the Japanese Association of Fatigue Science which works closely with the Japanese Ministry of Health, published its definition, and diagnostic and treatment criteria for ME / CFS. Leading Japanese researchers and doctors were involved in this. It's defintion included immune system, neurological, endocrine and infectious factors. It was similar to the Canadian Consensus criteria (2003) and the later International Consensus criteria (2011). Though, the Japanese definition goes into a bit more detail. The Japanese Ministry of Health funds scientific research into the factors defined by the Japanese Association of Fatigue Science in their definition. Their defintion is being used in Japan at present. See papers below:
Chronic Fatigue Syndrome Hirohiko Kuratsune, Yasuyoshi Watanabe. Fatigue Science for Human Health 2008, pp 67-88
Position paper - http://www.med.or.jp/english/pdf/2006_01/019_026.pdf

In Japan there is also a condition called called "Low natural killer cell syndrome" which is very similar to ME and CFS. Natural killer cell abnormalities are one of the most consistent findings in ME. The following papers outline the Japanese position on the illness. They correlate to some points in the aforementioned diagnostic criteria used by the Canadian and Norwegian governments.
- Aoki T, Usada Y, Miyakoshi H: A novel immunodeficiency: Low NK syndrome (LNKS).  Jap J Med 3212:14-17, 1985
- Aoki T, Usuda Y, Miyakashi H, et al: Low natural syndrome: clinical and immunologic features. Nat Immun Cell Growth Regul 6:116-128, 1987
- Aoki T, Miyakoshi H, and Usada Y et al: Low NK syndrome and its relationship to chronic fatigue syndrome. Clin Immunol Immunopathol. 69:253-65, 1993.

The clinical features of low natural cell numbers, function and cytotoxicity is specific to ME and CFS and "Low natural killer cell syndrome"

The diagnostic criteria used by the Canadian, Australian and Norwegian governments and health authorities represent best international practises and the latest medical and scientific research findings. They also integrate the 'Low natural killer cell syndrome' findings used by the Japanese government into their criteria.

The scientific and medical evidence show that ME is a highly complex physical illness, involving multiple factors, encompassing immune system, endocrine system, mitochondria, brain and nervous system dysfunctions and abnormalities, and this is accompanied in most cases by chronic viral and / or pathogen infections at some stage of the illness.

Introductory Lectures by Medical Doctors and Scientists

Paper by Dr. Anthony Komaroff, Professor of Medicine at Harvard Medical School in the USA. He has been treating ME / CFS patients and researching the illness since 1987. He is an internationally recognised ME expert. He has advised several Federal Bodies in the USA on the subject of ME / CFS over the years.

Research findings by Dr. Ronald W Davis, a top scientist in the USA and Professor at Stanford University. He is working with a few Nobel Prize winners at the Open Medicine Foundation ( www.openmedicinefoundation.org ) to discover the biological causes and pathology of ME / CFS, it's diagnostics and treatments.

and http://www.meaction.net/2017/02/22/stanford-team-announces-breakthrough-in-mecfs-research/

  Dr. Kenny De Meirleir is medical doctor based in Belgium and in Nevada in the USA. He runs a well known medical clinic in Belgium and also works for the Whittemore Peterson Institute in Nevada in the USA. He has been treating ME / CFS patients and researching the illness since 1990. He has seen thousands of ME / CFS patients over the years. The medical and scientific findings of Dr. Kenny De Meirleir over 20 years support the role of infections and immune system abnormalities in ME / CFS. Lecture series by Dr. Kenny De Meirleir videos 1 - 20, created in 2012 and 2013. Specifically for medical doctors and hospital consultants and scientific researchers.


Serious Illness
The potent combination of immune dysfunction and multiple infections, mitochondria and Krebs cycle malfunction, Neurological dysfunctions, Cardiac, Endocrine and HPA axis dysfunction cause a patient to become very exhausted and weak over time. Many ME sufferers end up bed-ridden, house bound or in wheelchairs. ME can be deadly, thousands of people around the world have died of ME and health complications caused by ME , see Memorial section. New research into causes of death in ME presents a very disturbing picture, click here to view findings
- Patient deaths from ME
- Why myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) may kill you: disorders in the inflammatory and oxidative and nitrosative stress (IO&NS) pathways may explain cardiovascular disorders in ME/CFS
- Suicide risk 5 times higher in ME/CFS : Poor medical care, neglect are major factors
- Medical Neglect & Ignorance causing patient deaths - In Remembrance: Emily Rose Collingridge

Comedians like Ricky Gervais have made fun of and mocked and laughed at such disabled people, and this is despicable, perverted, and disgraceful. There should be standards, ethics and laws in the entertainment industry to strongly discourage and punish such behaviour.

ME bears a resemblance to Cancer and AIDS in the sense that many ME patients have died of opportunistic infections, heart failure and certain cancers due to a depleted immune system and high levels of oxidative stress (and it's effects). Research has recently shown that most ME patients have serious heart and vascular abnormalities arising from ME , making them highly susceptible to a sudden heart attack. ME patients have died prematurely of heart attacks, and this is a continuing and worrying pattern of the illness. There is also a high rate of suicide among ME patients, this being brought about by frustration, desperation for some cure, social isolation, lack of support, constant pain, exhaustion and weakness, and financial hardships.

On 15th October 2009, Professor Nancy Klimas, then Professor of Medicine, Microbiology and Immunology at the University of Miami, famously said in the New York Times: “I hope you are not saying that (ME)CFS patients are not as ill as HIV patients.  I split my clinical time between the two illnesses, and I can tell you that if I had to choose between the two illnesses I would rather have HIV”. Dr. Nancy Klimas, is an internationally respected doctor and Immunologist and an expert in both ME / CFS and AIDS.
"There is evidence that the patients with this illness experience a level of disability that is equal to that of patients wi th late - stage AIDS, patients undergoing chemotherapy (and) patients with multiple sclerosis"
Professor Nancy Klimas, University of Miami, speaking at the launch of the US CDC campaign to raise awareness of ME/CFS, 3 November 2006, National Press Club, Wa shington DC

In 1995, Professor Mark Loveless, Head of the AIDS and ME/CFS Clinic at Oregon Health Sciences University said in his US Congressional Briefing that an ME/CFS patient: “feels effectively the same every day as an AIDS patient feels two weeks before death; the only difference is that the symptoms can go on for never-ending decades. Mr. Loveless supported his statement with data from research conducted at his own institution and morididity data provided by other ME experts who had compared the two diseases (AIDS and ME ).

In 1994, Dr. Anthony Komaroff of Harvard Medical School reported that the brains of those people with ME/CFS were identical to those with AIDS dementia, when viewed with SPECT imaging. They were both completely different to normal healthy brains. He believed that ME/CFS cases were the result of viral infection of the brain and nervous system, similar to AIDS.
SPECT imaging of the brain: comparison of findings in patients with chronic fatigue syndrome, AIDS dementia complex, and major unipolar depression. Schwartz R , Komaroff AL, Garada BM, Gleit M, Doolittle TH, Bates DW, Vasile RG, Holman BL. AJR Am J Roentgenol. 1994 Apr;162(4):943-51.

"There is no question in my mind that this is a physical disorder. The fact that we haven‘t been smart enough or invested enough in it to sort that, doesn’t mean that this is anything else."
Professor Dr. Ian Lipkin, Columbia University. He is internationally recognized as an authority on the use of molecular methods for pathogen discovery. Dr. Lipkin has over 30 years of experience in diagnostics, microbial discovery and outbreak response, has mentored and trained more than 30 students and post-doctoral fellows and leads a team of over 65 investigators, post-doctoral fellows and research and support staff in New York City and another 150 across the world. https://www.mailman.columbia.edu/people/our-faculty/wil2001

In September 2012, Dr Sandra Kweder of the FDA in America called ME/CFS "a serious or life threatening disease".

In 1994, one of the world’s most renowned ME/CFS clinicians, Dr Daniel L Peterson from the US, went on record: “In my experience, it is one of the most disabling diseases that I care for, far exceeding HIV disease except for the terminal stages (Introduction to Research and Clinical Conference, Fort Lauderdale, Florida, October 1994; published in JCFS 1995:1:3-4:123-125).

In 2004, Dr William Reeves, Chief of the ME/CFS research programme at the US Centres for Disease Control, (CDC) reported that ME/CFS patients “are more sick and have greater disability than patients with chronic obstructive lung or cardiac disease, and that psychological factors played no role (Press Release, AACFS, 7th October 2004).

Also in 2004, a randomised clinical trial found “In comparison with other chronic illnesses such as multiple sclerosis, end-stage renal disease and heart disease, patients with (ME)CFS show markedly higher levels of disability (Am J Occup Ther 2004:58:35-43).

In 1990, Dr. Nancy Klimas published a research paper in the Journal of Clinical Microbiology, in it she reported that the array of immunological defects in ME suggests that it is a form of acquired immuno-deficiency (Nancy Klimas, et al "Immunologic abnormalities in Chronic Fatigue Syndrome", Journal of Clinical Microbiology, 28, (June 1990)

The following document contains Important quotes from medical doctors, ME & CFS experts, scientific researchers, and others

Dr. Paul Cheney (who has successfully treated hundreds of ME patients) stated "These patients look a lot more like multiple sclerosis (MS) patients or AIDS dementia patients, whose dysfunctions are also subcortical".

On the Sickness Impact Profile Scale (SIPS), ME patients test as high or higher than people with Cancer and heart attack (Oslers Web, by Hillary Johnson, Penguin Books 1997, page 292).

According to research in 2015, Quality of Life measurements for ME patients were lower than those suffering Cancers, Depression Rheumatoid Arthritis, Schizophrnia, diabetes, heart diseases. See the chart below. The lower quality of life for ME patients is a major contributing factors to the high rate of suicide for ME patients.


Source: The Health-Related Quality of Life for Patients with Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS). Hvidberg et al. 2015. Plos One. DOI: 10.1371/journal.pone.0132421

The following passage from the book 'Osler's Web' by Hillary Johnson depicts the devastating effect of ME on people

Source: Osler's Web: Inside the Labyrinth of the Chronic Fatigue Syndrome Epidemic
by Hillary Johnson BLackinprint.com. 2006. Chapter: Gray Hats. Page 674.

The Face of ME

  • The following Facebook message and petition by an ME/CFS advocate outlines the problem faced by many patients, particularly severe ME cases


ill ME / CFS patient being taken to hospital.

The Documentary 'I Rememeber ME' provides a very emotional account of the effects of ME (CFS) on individuals, families and communities across the USA. The failures of government and the Federal health bodies are very apparent. It can be viewed on the following link - http://www.youtube.com/watch?v=401--WCB5dc

Another documentary film shows the effects of severe ME (CFS). More information about this documentary can be found at http://www.methehiddentruth.com/


The Courage of Patients

The film 'Unbroken' which is a major success in North America and Europe was based on a book written by Laura Hillenbrand who has ME (CFS). It depicts an American hero, Louis Zamperini, who overcame great adversity prior to and during world war 2.
Louis Zamperini read Laura Hillenbrand's other book 'A Sudden Illness' and he was deeply impressed by her courage in fighting the illness ME (CFS). He was so impressed by her bravery that he gave her his own Purple Heart medal which he won in the second world war. I have attached the letter with Purple Heart medal. The Purple Heart is only given for acts of great bravery which also involve personal injury in the act. Today Laura Hillenbrand owns this Purple Heart medal, to show great courage in the face of a terrible and painful illness, ME (CFS), and a determination to overcome and defeat this illness.

CBS news interviewed Laura Hillenbrand below. She explains her illness and what she has endured over 3 decades.

 

Fox News Interview - http://www.foxnews.com/on-air/fox-news-sunday-chris-wallace/videos#p/158303/v/3963255832001


The Problems of Misdiagnosis and Missed Diagnosis
These are the biggest problems faced by the medical community worldwide. ME Research UK found that misdiagnosis is very common in ME and CFS and published their findings online at http://www.meresearch.org.uk/information/publications/misdiagnosis-on-a-grand-scale/

Dr. Byron Hyde is a medical doctor based in Canada. He has been treating ME / CFS patients and researching the illness since 1986, and he has seen thousands of ME / CFS patients. Dr. Hyde is an internationally recognised ME expert and has contributed much to research, and clinical practise methodologies, including the Canadian Consensus Criteria 2003 and International Consensus Criteria 2011. The following video lecture by him provides an overview of the problem of misdiagnosis. His medical textbook (below) for ME and CFS provides an in-depth account of the problems of misdiagnosis and missed diagnoses. It also reveals innovative medical methods for properly diagnosing and treating the illness




Population Prevalence &
Epidemiology

The ME Primer for Healthcare Professionals: based on Myalgic encephalomyelitis: International Consensus Criteria, 2012 puts the figure between 0.4 - 1%.

There are 45,812 ME sufferers in Ireland using the 1% finding from the ME Primer for Healthcare Professionals: based on Myalgic encephalomyelitis: International Consensus Criteria, 2012 and some other international studies. There are 3.16 million Americans afflicted with ME. In Britain, it is estimated that 623,000 people have ME, and 5 million people in the European Union have ME based on the 1% finding (ME Primer for Healthcare Professionals: based on Myalgic encephalomyelitis: International Consensus Criteria, 2012).

It is important to note that some ME sufferers have been diagnosed properly using modern and accurate diagnostic criteria and many have not been diagnosed due to lack of knowledge of the illness and / or poor diagnostic methods and equipment in their state / country. It is estimated that 50% or more of people with ME have been undiagnosed with the illness and suffer from an illness they are unaware of. As more modern and accurate diagnostic criteria become accepted by governments and medical authorities, and diagnostic tests and equipment become more advanced and accurate and as doctors become more educated about this illness and specialist clinics become operational, and public awareness of the illness increases, there will be an increase in the number of people diagnosed with this illness. Applying this 1% finding to the global population would suggest that 70,000,000 people have this illness. Though global regional differences may exist due to varying toxic exposures, pathogen exposures, allergen exposures, lifestyle stress factors, pollution of foods, liquids and air, and other illness initiating factors. Population prevalance is discussed in more detail in the 'Why set up a Clinic' section on this web site.

There have been well documented ME epidemics and outbreaks throughout history. These include the following:

1917 Van Economo reports an illness involving brain and neurological inflammation, weakness, and great fatigue and some deaths. See paper 'New Clinical Entity' published in the Lancet in 1956.
1918 - 1924, several outbreaks of an illness involving brain and neurological inflammation, weakness, and severe fatigue reported throughout Europe. See paper 'New Clinical Entity' published in the Lancet in 1956.
1924 England and Wales 5,039 cases of encephalitis lethargica. See paper 'New Clinical Entity' published in the Lancet in 1956.
1934 Los Angeles County Hospital. Called 'Atypical Poliomyelitis'
1936 Fond Du Lac, Wisconsin - St. Agnes Convent - Encephalitis
1937 Erstfeld, Switzerland - Abortive Poliomyelitis
1937 St. Gallen, Switzerland - Frohburg Hospital Abortive Poliomyelitis
1939 Middlesex, England - Harefield Sanatorium
1939 Degersheim, Switzerland - Abortive Poliomyelitis
1945 Pennsylvania. Hospital of the University of Pennsylvania - epidemic Pleurodynia
1946 Iceland disease resembling Poliomyelitis with the character of Akureyri disease
1948 Iceland, North Coast towns - epidemic simulating Poliomyelitis
The outbreak in Iceland was important, and provided some vital clues about the illness.
"However, children in epidemic Neuromyasthenia areas responded to poliomyelitis vaccination with higher antibody titres than in other areas not affected by the poliomyelitis epidemic, as if these children had already been exposed to an agent immunologically similar to poliomyelitis virus (Sigurdsson, Gudnad6ttir Petursson, 1958). Thus, the agent responsible for epidemic Neuromyasthenia would appear to be able to inhibit the pathological effects of poliomyelitis infection. When an American airman was affected in the 1955 epidemic and returned home, a similar secondary epidemic occurred in Pittsfield, Massachusetts, U.S.A. (Hart, 1969: Henderson and Shelokov, 1959)."
Many outbreaks of ME or epidemic Neuromyasthenia worldwide followed an outbreak of polio virus.
Parish JG (1978), Early outbreaks of 'epidemic neuromyasthenia', Postgraduate Medical Journal, Nov;54(637):711-7, PMID: 370810.
1948 300 sporadic cases of epidemic Neuromyasthenia seen in South California between 1948 and 1965.
1949 Adelaide, South Australia - a disease resembling Poliomyelitis
1949 Cambridgeshire, England - aberrant poliomyelitis. Involvement of other Enteroviruses suspected.
1950 Louisville, Kentucky -- St. Joseph 's Infirmary - epidemic Neuromyasthenia
1950 Upper State New York -- outbreak resembling the Iceland disease, simulating " acute Anterior Poliomyelitis
1952 London, England - Middlesex Hospital Nurses ' Home - Encephalomyelitis associated with Poliomyelitis virus
1952 Copenhagen, Denmark - epidemic Myositis
1952 Lakeland, Florida - epidemic Neuromyasthenia
1953 Coventry and District, England - an illness resembling Poliomyelitis observed in nurses
1953 Rockville, Maryland - Chestnut Lodge Hospital - Poliomyelitis-like epidemic Neuromyasthenia
1953 Jutland, Denmark - epidemic Encephalitis with vertigo
1954 Tallahassee, Florida - epidemic Neuromyasthenia
1954 Seward, Alaska - benign Myalgic Encephalomyelitis (Iceland Disease)
1954 Berlin, Germany - British army - further outbreak of a disease resembling Poliomyelitis
1954 Liverpool, England - outbreak among medical and nursing staff in a local hospital
1954 Johannesburg, South Africa - epidemic Neuromyasthenia
1955 Dalston, Cumbria, England epidemic and sporadic outbreak of an unusual disease
1955 London, England - Royal Free Hospital - outbreak in staff and patients of Benign Myalgic Encephalomyelitis
1955 Hampstead, London
1955 Perth, Australia - virus epidemic in waves
1955 Gilfac Goch, Wales - outbreak of benign Myalgic Encephalomyelitis
1955 Durban City, South Africa - Addington Hospital. Outbreak among nurses called 'Durban Mystery Disease' also called 'epidemic Neuromyasthenia'
1955 Segbwema, Sierra Leone - outbreak of Encephalomyelitis
1955 Patreksfjorour and Porshofn, Iceland - unusual response to polio vaccine
1955 Northwest London, England - nurses ' residential home - acute Infective Encephalomyelitis simulating poliomyelitis
1956 Ridgefield, Connecticut - epidemic Neuromyasthenia
1956 Punta Gorda Florida - outbreak of epidemic Neuromyasthenia
1956 Newton-le-Willows, Lancashire, England - Lymphocytic Meningoencephalitis with myalgia and rash
1956 Pittsfield and Williamstown, Massachusetts - benign Myalgic Encephalomyelitis
1956 Coventry, England - epidemic malaise, benign Myalgic Encephalomyelitis
1957 Brighton, South Australia - Cocksakie Echo virus Meningitis, epidemic Myalgic Encephalomyelitis
1958 Athens, Greece - nurses ' school - outbreak of benign Myalgic Encephalomyelitis with periostitis and arthopathy noted.
1958 Southwest London, England - reports of sporadic cases of Myalgic Encephalomyelitis
1959 Newcastle Upon Tyne, England - outbreak of benign Myalgic Encephalomyelitis
1961 Basel, Switzerland - sporadic cases of benign Myalgic Encephalomyelitis
1961 New York State - outbreak of epidemic Neuromyasthenia in a convent
1964 Northwest London, England - epidemic malaise, epidemic Neuromyasthenia
1964 Franklin, Kentucky - outbreak of Neuromyasthenia in a factory
1965 Lamarque, Texas, U.S.A. - epidemic Neuromyasthenia. Investigated by Leon-Sotomayor (1969).
1967 Edinburgh, Scotland - sporadic cases resembling benign Myalgic Encephalomyelitis
1968 " Fraidek, Lebanon - benign Myalgic Encephalomyelitis
1969 Brooklyn, New York - State University of New York Downstate Medical Center - epidemic Neuromyasthenia, unidentified symptom complex
1970 Lackland Air Force Base, Texas - epidemic Neuromyasthenia
1970 London, England - Great Ormond Street Hospital for Children - outbreak of Neuromyasthenia among nurses
1975 Sacramento, California - Mercy San Juan Hospital - Infectious Venulitis, epidemic " Phelobodynia
1976 Southwest Ireland - epidemic Neuromyasthenia, benign Myalgic Encephalomyelitis
1977 Dallas Fort Worth, Texas - epidemic Neuromyasthenia
1979 Southampton, England - Myalgic Encephalomyelitis
1980 West Kilbridge, Ayrshire, Scotland - epidemic Myalgic Encephalomyelitis
1980 San Francisco, California epidemic persistent flu-like illness
1981 Stirlingshire, Scotland - sporadic Myalgic Encephalomyelitis
1982 West Otago, Dunedin and Hamilton, New Zealand - Myalgic Encephalomyelitis
1983 Los Angeles, California - initial cases of an unknown, chronic symptom complex involving profound "fatigue"
1984 Lake Tahoe Area of California/Nevada - start of a yearlong epidemic involving " over 160 cases of chronic illness eventually characterized as Chronic Fatigue Syndrome
Source: Paradigm Change web site

- see History of ME presented by Lisa Petrison to the CFSAC in 2014
- Dr. Byron Hyde's analysis of ME Epidemics
- Parish JG (1978), Early outbreaks of 'epidemic neuromyasthenia', Postgraduate Medical Journal, Nov;54(637):711-7, PMID: 370810. 'Epidemic Neuromyasthenia' was used to describe ME in the past.

The Views and Lectures by Leading Medical Doctors in the Field

Professor Anthony Komaroff M.D. of Harvard Medical School

has recently written the following:

(1) many patients with ME / CFS have no diagnosable psychiatric disorder and that ME / CFS is not a form of depression; 

(2) there is a state of chronic, low-grade immune activation, with evidence of activated T cells and evidence of genes reflecting immune activation, as well as evidence of increased levels of cytokines; 

(3) there is substantial evidence of poorly-functioning NK cells (white blood cells that are important in fighting viral infections); 

(4) there is evidence of white and grey matter abnormalities in the brain;

(5) there is evidence of abnormalities in brain metabolism (and evidence of dysfunction of energy metabolism in the mitochondria); 

(6) there is evidence of abnormalities in the neuroendocrine system, particularly in the HPA axis but also in the hypothalamic-prolactin axis and in the hypothalamic-growth hormone axis; 

(7) there is evidence of cognitive difficulties, especially with information processing, memory and/or attention; 

(8) there is evidence of abnormalities in the autonomic nervous system (including a failure to maintain blood pressure, abnormal responses of the heart rate, and unusual pooling of blood in the legs, as well as low levels of blood volume); 

(9) there is evidence of disordered gene expression, especially in those genes that are important in energy metabolism and in genes connected to HPA axis activity, to the sympathetic nervous system and to the immune system; 

(10) there is evidence of frequent infection with viruses, especially herpesvirus and enteroviruses.

Source: Summer 2008 issue of The CFIDS Chronicle published by The CFIDS Association of America.

Lecture by Dr. Dan Peterson providing a medical and scientific overview of ME / CFS (Stockholm, November 2011). Dr. Dan Peterson, a medical doctor has been treating ME / CFS patients since the mid 1980's and is an internationally acclaimed ME doctor and expert. (4 continuous videos of his lecture below)







 

Slides of Dr. Peterson's lecture at ME/CFS conference in Sweden, 2011


Lecture on ME / CFS by Dr. Byron Hyde, Winter 2012

 

Dr Harvey Alter, who discovered the hepatitis C virus, and works in the US National Institutes of Health (one of the top research institutes in the world) said in 2010: “I’m absolutely convinced that when you define this disease by proper criteria, this is a very serious and significant medical disease, and not a psychological disease.  It has the characteristics of a viral disease” 

Professor Luc Montagnier (who won the Nobel prize for discovering the AIDS virus) said: “Scientists have already uncovered a lot about ME, but this information does not reach professional healthcare personnel, and the disease is not taken seriously.  It is about time this changes” 

Names and Definitions - Understanding the Confusion in the Field

'Remember in describing the Lake Tahoe epidemic this (Holmes) committee were describing a typical Myalgic Encephalomyelitis Epidemic.'
Source: A Brief History of Myalgic Encephalomyelitis, by Dr. Byron Hyde

ME is often called CFS or Chronic Fatigue Syndrome. The term 'Chronic Fatigue Syndrome' was invented by Mr. Stephen Straus of the NIH in 1987 to describe an ME type illness and recent ME type epidemic in Lake Tahoe. Prior to 1987 there was no such thing as 'Chronic Fatigue Syndrome' or CFS. In 1987 and 1988, the CDC came under great pressure to investigate this ME type epidemic, which they did. The findings of medical doctors from Lake Tahoe were presented to the CDC at the time, and the CDC also carried out an investigation and gathered it's own data, and all of these findings (by doctors and the CDC) were published in scientific papers at the time. According to doctors and scientists, the Lake Tahoe epidemic had all the characteristics of an ME epidemic. Though some researchers and doctors called it Chronic Epstein Barr virus Syndrome (CEBV) at the time. This term became obsolete as a minority of patients had active EBV or reactivated EBV and some had other viruses and pathogens and immune system deficiencies.

In 1988, the Holmes committee of the CDC met to define the illness, but it became bitterly divided over what to call this illness, some favoured the medical term Myalgic Encephalomyelitis (ME) as it had most of the characteristics of this illness, while others disagreed. If the Lake Tahoe epidemic had occurred in Britain, the term Myalgic Encephalomyelitis (ME) would have been used, as evidenced by past epidemics and outbreaks there. But, Dr. Straus favoured the term he himself recently invented 'Chronic Fatigue Syndrome', and a definition which was loose and ambiguous, and he managed to manipulate a few others on the committee to support him. Some doctors, including Dr. Parish abd Dr. Shelokov disagreed with Straus and quit the CDC committee and refused to sign off on the final name and definition. It was agreed to temporarily call the illness 'Chronic Fatigue Syndrome' and a decision was made to await further scientific studies, in order to arrive at a more comprehensive and final definition with biomarkers and biological evidence. Thus the very term or name 'Chronic Fatigue Syndrome' was meant to be temporary. Other factors also played a part in the CDC's final decision to label it 'Chronic Fatigue Syndrome', this included intense lobbying and pressure on national and state politicians by business owners in the Lake Tahoe area and Nevada state who wished to have this illness disappear or be labelled a non illness ; this is discussed in the book A Brief History of Myalgic Encephalomyelitis, by Dr. Byron Hyde. Business interests played a key role in this, yet ironically the families of some business owners later became ill with CFS, and suffered the consequences of this ill defined name and definition.

Dr. Byron Hyde's book, A Brief History of Myalgic Encephalomyelitis , details the activities of the Holmes Committee, and how it came to invent the term 'Chronic Fatigue Syndrome'. He also mentions the errors, misunderstandings and deficiencies which occurred in the creation of such a misleading term and definition. The book uses the findings and evidence from prior ME epidemics to support the case for caling the Lake Tahoe illness ME or ME type illness.

The medical and scientific findings from the Lake Tahoe epidemic were important in the late 1980's and early 1990's, and they are still relevant today. Some of the largest studies into ME / CFS were conducted during the mid to late 1980's and 1990 & 1991. We have collated these findings on the following page www.me-ireland.com/lake-tahoe.htm . The US government failed to follow up the viral, bacteria and mycotoxin, immune dysfunction, neurological, brain, and endocrine evidence from this Lake Tahoe epidemic and the Lyndonville epidemic (1985-1986) and outbreaks in other states in the 1990's. This failure by government continued throughout the late 1990's and 2000's, and this created a lack of biomarker criteria for medical doctors and scientific researchers to work with. The scientific studies, recommended by the CDC in 1988 were not carried out or not properly funded by the US government. Most importantly replication studies were not carried out. In 1990 research into ME/CFS revealed retrovirus sequences in patients suggesting retrovirus and possible HTLV infection - HTLV virus infection in CFS patients . This was ground breaking at the time, but it was not properly replicated by the CDC and NIH, and by other researchers and bodies. Dr. DeFreitas and the Wistar Institute offered to bring a CDC team of researchers to their lab to show them how they detected the retrovirus in ME patients. The CDC refused this offer. This neglect of important scientific findings was unexpected and quite surprising at the time. The CDC tried to suppress the retrovirus findings, dismissed and ridiculed the findings of Defreitas and others, tried to get DeFreitas fired from her job, and they discouraged and blocked other researchers from verifying her findings. This exposed a rather sinister agenda to suppress, destroy and undermine science. The financial scandal in the CDC where millions of dollars for CFS research went missing, and were criminally and fraudalently used to research other illnesses and activities, showed the corruption, dishonesty, and suppression existent inside the CDC.

Dr. Michael Holmes in New Zealand found evidence of retrovirus infection in ME patients in the late 1980's and 1990's. He found reverse transcriptase, cells with convulted nuclei similar to AIDS, high levels of interferon and T cell abnormalities in ME patients - all suggesting retrovirus infection. His research work was suppressed and not funded after the CDC condemned DeFreitas in the USA. In 1994, Dr. Anthony Komaroff of Harvard Medical School reported that the brains of those people with ME/CFS were identical to those with AIDS dementia, when viewed with SPECT imaging. They were both completely different to normal healthy brains. He believed that ME/CFS cases were the result of viral infection of the brain and nervous system, similar to AIDS. (SPECT imaging of the brain: comparison of findings in patients with chronic fatigue syndrome, AIDS dementia complex, and major unipolar depression. Schwartz R , Komaroff AL, Garada BM, Gleit M, Doolittle TH, Bates DW, Vasile RG, Holman BL. AJR Am J Roentgenol. 1994 Apr;162(4):943-51.). Dr. Seymour Grufferman and Dr. William Blattner found some evidence of HTLV infection in ME patients from the North Carolina Symphony in the early 1990's (Osler's Web, Hilary Johnson, pages 651-652). This was not followed up by the CDC and NIH.

In her book Plague , Dr. Judy Mikovitts managed to isolate a retrovirus in most ME patients, and she itemised the structure, operations and genetic material of this retrovirus. This retrovirus was a gamma retrovirus and was similar but different to the xmrv virus identified by Dr. Silverman. Researchers searched for Silverman's xmrv virus but failed to look for Mikovitt's gamma retrovirus. They found xmrv contamination. Researchers failed to use the exact methodologies used by Dr. Judy Mikovitts to isolate and study her gamma retrovirus, and thus they failed to find this gamma retrovirus in follow up studies, and this created some international controversey which has yet to be fully resolved. In 2013, Dr. Sidney Grossberg isolated a gamma retrovirus similar to Mikovitts's retrovirus, and he named it JHK virus. He has supplied details and methods for isolating this virus in ME patients and others. In October 2013, Dr. Hornig and Dr. Lipkin of Columbia University found retroviral sequences in ME/CFS patients, which corroborates the earlier findings of Mikovitts, De Freitas, Cheney, Peterson and Buchwald, surprised them and some other people. Yet 23 years ago, researchers found retrovirus sequences, and sadly these were never followed up and replicated properly. The implications of Defreitas', Holmes', Mikovitts', Cheney's Peterson's, Grossberg's, Lipkins' findings are very serious, there are undiagnosed retroviruses infecting the general population, and possible co-infections causing serious illness to many people. This is of great public concern. Dr. Judy Mikovitts and other scientists and doctors continue to push for further scientific research into retroviruses and the deployment of diagnostic kits and treatments. This failure to properly investigate retrovirus infections in ME patients, particularly severely ill patients, was a gross failure by government and has had serious repercussions for US citizens and millions of people worldwide.

During the late 1980's a new virus was discovered and called Human Herpes Virus 6a, and this infection was found in a significant percentages of CFS patients in studies at the time, and ever since. Yet the CDC, NIH and HHS failed to follow up these findings, replicate them across America and other countries, and establish causalities between immune dysfunctions and viral infections, and integrate them into the definition, diagnostics and biomarker data for CFS. The NIH and Department of Health also failed to encourage hospitals, clinics and labs to update their diagnostic equipment and methods to identify these new viruses. They also ignored growing evidence of toxic molds and mycotoxins in damp buildings and the fact that many people with CFS and respiratory illnesses had these infections. Thus the government failed on many counts to take basic measures to safeguard the health and well being of millions of Americans.

By 1994, the CDC published the Fukuda defintion and this created more confusion, as it lacked biomarkers, scientific evidence, replicated studies, clinical evidence and accurate diagnostics. This Fukuda criteria was so broad in its terms that it encompassed other similar illnesses. This in turn created different patient sets with different illnesses, all called CFS. This created heterogenous groups and conflicting research results, as one had different illnesses under one banner. After 1994, the US government was lobbied to clarify the situation and carry out intensive scientific research into CFS by several scientists, medical doctors and patient organisations, but the government neglected to do this on an adequate scale. By the mid to late 1990's, big insurance companies played a part in lobbying politicians and government health bodies to state CFS was a non illness and that it was psychiatric, in order to save money by not paying for patient diagnosis and treatments. This destroyed the lives of many patients and their families.

Certain individuals in the NIH and CDC played a part in blocking funding for CFS research during this period, as they both thought it was not worth researching. Dr. Bill Reeves of the CDC turned whistleblower in the late 1990's and said the following about fraud and misallocation of monies for CFS research:
“I believe that CDC has intentionally misrepresented monies allocated to CFS research and I cannot ethically support this,” wrote Dr. Reeves in his public statement. “The misrepresentations involve systematically charging between $400,000 and $2 million incurred by unrelated activities to CFS between 1995-97 and reporting to DHHS [Department of Health and Human Services], Congress and patients that the monies were used for CFS research.”

A 1999 report from the Inspector General of HHS found that of the $22.7 million the CDC charged to its CFS program between 1995 and 1998, less than half was spent on the illness. The report stated: “CDC spent significant portions of CFS funds on the costs of other programs and activities unrelated to CFS and failed to adequately document the relevance of other costs charged to the CFS program…As a result of these inappropriate charges, CDC officials provided inaccurate information to Congress regarding the use of CFS funds.” The Inspector General’s report found that $8.8 million was spent on non-CFS projects and that the documentation on an additional $4.1 million was so poor that it was impossible to determine whether they were used to support CFS research or not.

From fiscal 1995 through fiscal 1997, some $5.8 million that the CDC told Congress had been spent on CFS research actually went to other activities. Certain members in the CDC tried to cover this up at the time. There were no criminal prosecutions and court cases, and no one was fired or resigned, which was unusual when one considers the seriousness of the crimes and the fact that Americans were dying of the illness. Furthermore, Dr. Byron Hyde the famous Canadian doctor stated in his booklet ( A Brief History of Myalgic Encephalomyelitis ) that Dr. Straus (NIH) may have played some part in misdirecting or misappropriating the $34 million designated by the US government for ME (CFS) research in the late 1980s' and early 1990's. The $34 million was spent on researching other illnesses. Thats over $40 million in total which went missing from ME (CFS) research and was a huge loss to ME (CFS) research.

This failing by the US government, in particular the CDC and the NIH created a vacuum in medical science and scientific research, which had devastating consequences for millions of Americans and their families and communities. This is detailed in the book Osler's Web: Inside the Labyrinth of the Chronic Fatigue Syndrome Epidemic. Over time, some research, mostly private research funded by patients, ME organisations, some medical doctors, foundations and some Universities, found significant biological abnormalities and dysfunctions in the immune system, HPA axis, brain and nervous system, autonomic system, heart and circulation and the mitochondria and chronic infections in some cases. They also found close biological correlations between CFS and ME. Yet these were not integrated into government policies and diagnostic and treatment criteria. The most fundamental question is this - Why was scientific and medical evidence of immune system dysfunctions and deficiencies, neurological and brain abnormalities, pathogen infections of the nervous system, muscles and intestines, mitochondria damage and dysfunctions, cardiac abnormalities, greater risks of specific Cancers, and HPA axis and endocrine abnormalities and dysfunctions ignored by the CDC, NIH, HHS and US government in the 1980's, 1990's and 2000's ?

The following Prime Time television programme was broadcast throughout the USA on the ABC channel in 1996. It outlined these facts to a national audience at the time.

 

A Bad and Misleading Term
The term 'Chronic Fatigue Syndrome' as defined by CDC is devoid of meaning, it is a useless, imprecise and ineffective term, it deliberately ommitted biomarkers and medical facts, and tells us nothing. It was invented by Dr. Straus (NIH) in 1987 to describe an ME type illness and recent ME type epidemic in Lake Tahoe. Yet it failed to describe the illness, define the illness or even name it properly.

Would one call Diabetes "Chronic Thirst Syndrome" or call Cancer "Chronic Weakness and Pain syndrome" or call Alzheimers disease "Chronic Forgetting Syndrome" or call Parkinsons disease "Chronic Tremor Syndrome" or call Anemia "Chronic Tiredness Syndrome" ?? The answer would be no as they are insulting, abusive and tell one nothing about the illness. Then why did Dr. Straus and some others use an insulting and abusive term such as "Chronic Fatigue Syndrome" to describe an ME type illness, an ME epdemic?

Dr. Straus' and Fukudas' CFS definition of 1994 was a disaster and lacked precision, accurate diagnostic critria and biomarkers and was so broad that it encompassed several other illnesses and created even more contradictions and confusion in the fields of medicine and scientific research. Calling ME all types of names whether it is 'Chronic Fatigue Syndrome', 'Chronic Weakness Syndrome', 'Chronic Headaches Syndrome' , 'Chronic Itch Syndrome', 'Chronic Coldness Syndrome', 'Chronic Pain Syndrome', etc. does not disguise the fact that it is ME or an ME type illness. This lack of precision, accuracy and specificity by the CDC, NIH and Dr. Straus meant that different illnesses were called CFS or ME, and this created heterogenous groups in research trials and medical practises, making it impossible to differentiate the genuine ME (cases) from the non cases. This confusion led to contradictory research findings, and to inconclusive markers for the illness. This in turn has led to contradiction and stagnation in scientific research and in medical / clinical practises, which exists to this day.

There is evidence that Dr. Straus acted maliciously to make the illness "evaporate" and disappear and become a non illness - click here to view letter exchanged between Dr. Straus and Dr. Fukuda shortly after the Fukuda definition was approved in 1994. He deliberately worked with others to omit the scientific and medical evidence, give the illness a bad name and a poor quality definition, belittle and denigrate it, deprive it of legitmacy and of research funding, and make the illness disappear. These actions contributed to the deaths of tens of thousands of patients. This was serious medical misconduct, possibly criminal.

Yet over time, the words CFS and ME were both used to describe the same illness, and it is customary to use one of the terms to describe the illness or a composite term such as ME / CFS. The term 'Chronic Fatigue and Immune Dysfunction Syndrome' or CFIDS is also used in the USA to describe the same illness. Using the term 'Chronic Fatigue' in the name of this illness is misleading, inaccurate and imprecise and has led to the illness being trivialised, mocked and belittled (even by some doctors). We have used the term ME on our web-site, though in some exceptional circumstances ME / CFS is used in order to cater for some patient organisations and past research papers.

If Dr. Stephen Straus (NIH) had decided to call the illness 'ME type illnesses' in 1988 and not CFS, and the NIH and CDC had properly researched the illness and funded global research into it, and other research institutions around the world copied them, the position would be much clearer for everyone today. We would have ME on the one hand and ME type illnesses which may have been named Neuro-Endocrine-Immune illness, Chronic HHV6a illness, Chronic Mold and Mycotoxin illness, Chronic Lyme disease with co-infections, Chronic Mycoplasma disease, Chronic Immune Dysfunction Syndrome or Chronic HTLV illness all of which would be separate to ME. Though all would share many symptoms. This would facilitate precise and accurate diagnostics and treatments of patients and make the work of doctors, health bodies, insurance companies and goverments easier and more effective.

Dr. Straus did nothing to remedy his own errors and he played an important part in blocking government sponsored biological research into ME (CFS) for many years. Dr. Byron Hyde the famous Canadian doctor stated in his booklet ( A Brief History of Myalgic Encephalomyelitis ) that Dr. Straus may have had some role in misdirecting or misappropriating the $34 million designated by the US government for ME (CFS) research in the late 1980s' and 1990's. The $34 million was spent on researching other illnesses. This was a huge loss to ME (CFS) research.

Britain
In Britain, the name ME was used, not CFS. This was the case from 1956 to the early 1990's. British doctors and the British medical organisations, European and American doctors and medical orgnaisations accepted the findings of top ME doctors such as Dr. Donald Acheson, Dr, Melvin Ramsay, Dr. John Richardson, Dr. E. O'Sullivan, Dr. Galpin, Dr. Deisher, Dr. Parish, Dr. Shelokov, Dr. Henderson, Dr. Sigurdsson, Dr. Poskanzer, Dr. Gsell, Dr. Hill, Dr. Dowsett and Dr. Behan. These doctors had many years experience diagnosing, treating and researching ME. Some doctors even carried out autopsies on dead ME patients to determne the pathological aspects of the disease. These medical doctors and reseachers accumulated detailed medical facts and evidence over a few decades.There was a consensus within the medical community worldwide as to what ME was, and what it involved. Diagnostics and treatments and research efforts revolved around infections, immune dysfunctions, neurological dysfunctions, endocrine dysfunctions, and muclo-skeletal abnormalities and mitochondria dysfunctions.

In 1970 two psychiatrists McEvedy and Beard published a paper claiming that M.E. was a psychiatric disorder and that it was "all in the mind". The authors of this paper did not physically examine the patients, did not interview the patients, did not consult with the medical doctors and medical records of the patients. They merely superficially reviewed a few studies. The paper was a fraud, and was not based on examination of patients and of biological and biomedical evidence and the biological testing and interview of patients. The paper was based on presumptions and assumptions. The paper provoked a furious backlash from medical doctors and nurses who fell ill with M.E. Doctors, nurses and patients wrote letters in to the British prress and to medical and scientific journals rejecting the hypothesis of McEvedy and Beard. In 1978, The Royal Society of Medicine rejected the paper of McEvedy and Beard and their presumptions and stated that ME was a physical, biological illness involving infection and neurological, immune system and endocrine abnormalities - British Medical Journal, June 1978. This settled the matter in Britain and remained the position of the British Medical authorities and British government until the early 1990's. Dr. Byron Hyde a famous Canadian medical doctor wrote an interesting account of this in the following booklet - A Brief History of Myalgic Encephalomyelitis.

Then in 1991 and the early 1990's, a few psychiatrists managed to hijack the term ME (CFS) and falsely claimed it to be psychiatric illness and "all in the mind". The following nefarious activities were undertaken by a few psychiatrists in Britain:

The consequences of this psychiatrist inolvement were severe for ME patients and their families, as many ME (CFS) patients were often refused disability payments by insurance companies and by government. The patients were deprived of lab tests, and biological testing, and kept in a limbo of sickness and deteriorating health for years and decades. This led to loss of jobs, income, education, dignity, self-esteem, and to family break ups, suicides, and premature deaths from the health complications of ME (CFS), etc. for patients. It was a type of war against ME patients, and the source of great controversey in medicine. The psychiatrists became very wealthy from these activities and their work for insurance companies, drug companies and for government bodies. This is discussed and analysed in more detail in the Bogus Treatments section of this web site. Biological research into ME (CFS) continues to be blocked or severely under-funded in several countries in the present day. Patients and doctors have had to rely on private scientific research funded by patients, ME organisations, some medical doctors, foundations and some Universities. Recently, there has been a change in the policies of some governments who are now funding some biological research into the immune dysfunctions, pathogen infections, neurological abnormalities, HPA dysfunctions, mitochondria defects, etc. in ME, and ignoring the advice and influence of some psychiatrists. Research is under funded in Europe and North America, read http://me-ireland.com/research2.htm

Versions of CFS
There are several versions of CFS, including the CDC version, Oxford version, NICE version, the Canadian Consensus version, the Nightingale version, Dr. Peterson's and Dr. Cheney's version, and they all contradict each other. The CFS version of Dr. Peterson and Dr. Cheney, the doctors who first diagnosed patients during the Lake Tahoe epidemic and witnessed the first outbreak of "CFS" is the most credible and complete version. They state that CFS is all of the primary determinants of ME plus the new evidence generated by Dr. Cheney and Dr. Peterson and the other scientific researchers and doctors who researched the Lake Tahoe epidemic from the mid 1980's to the early 1990's. This evidence has been gathered and presented on the Lake Tahoe Epidemic (1984 - 85) page on this web site

Their definitions of the illness were accurate and contained biomarkers, and have continued to be relevant in medical and scientific terms. These biomarkers and other biomarkers were found in subsequent research studies and patient cases. CFS closely resembled an ME type epidemic and had all of the factors of ME and additional biological factors, possibly to do with geographical location. It was a distinct biological illness with subgroups. Research provided additional information and insights over the years, corroborating and adding to the findings of Dr. Cheney and Dr. Peterson. Unfortunately the CDC and NIH deliberately ignored their scientific findings and biomarkers for many years. Drs. Peterson and Cheney's findings and definitions and further follow up findings by other researchers were used in several successful CFS and ME clinics in the USA and abroad. They also played a key role in the development of the Canadian Consensus criteria 2003 and International Consensus criteria 2011, which are widely considered best international practises for diagnosing and treating the illness.

Chronic Fatigue in a larger context
The larger problem of 'Chronic Fatigue' from diagnosed and undiagnosed illnesses such as Diabetes, Cancer, MS, cardiac disease, adrenal disease, thyroid disease, Lyme disease, Vasculitis, parastical infections, AIDS, nutritional deficiencies (also in developed countries), heavy metal toxicity, organophosphate poisoning etc. which cause great fatigue and weakness remains a problem in many countries. Bierl et al. (1) found that 12% of the American population suffer from chronic fatigue which may be caused by one of these aforementioned illnesses or by a progression to a disabling illness, while 1.2% suffer from ME. The great problem is that many are undiagnosed and many people suffer unnecessarily. Doctor surveys consistently show that over 50% of patients complain of great fatigue while attending their doctor. The diagram below presents this problem of 'Chronic Fatigue' as it exists in many societies. ME is one of many physical, biomedical illnesses which involve 'chronic fatigue'. The term 'chronic fatigue' is far too general, and too easily open to misinterpretation and mis-diagnosis. It is important to differentiate which illness the patient actually suffers from.

"Severe intractable fatigue is endured by many people with a wide range of neuro-inflammatory, neuropsychiatric, and autoimmune disorders and cancer. Pathological fatigue is experienced by between 59 and 100 % of cancer sufferers depending on the clinical status of the disease [1]. Severe chronic fatigue is also experienced by many people with an autoimmune disease with 67 % of people with Sjögren’s disease [2], up to 76 % of patients with systemic lupus erythromatosis (SLE) [3] and upwards of 70 % of people with rheumatoid arthritis [4] suffering incapacitating levels of fatigue. Upwards of 80 % of multiple sclerosis patients suffer from incapacitating fatigue [5]. Beiske and Svensson reported that between 37 and 57 % of patients with Parkinson’s disease experience incapacitating fatigue [6]. Winward et al. reported data which strongly indicates that fatigue in stroke victims is a direct consequence of the cerebral infarct and not merely a consequence of increased effort during rehabilitation [7]. Severe fatigue was experienced by 87 % of people following major stroke 56 % of people following minor stroke and 29 % of people following a TIA [7]. Fatigue is commonplace in people following a myocardial infarction with almost 100 % of patients reporting debilitating levels of exhaustion. Interestingly, many patients reported severe fatigue without any concomitant signs of depression [8]. "
Source: The Neuro-Immune Pathophysiology of Central and Peripheral Fatigue in Systemic Immune-Inflammatory and Neuro-Immune Diseases Morris et al. 2015.

There are common factors in all of these illnesses, involving activated immune pathways and inflammatory cytokines and inflammatory markers, and neuroinflammation, and high oxidative and nitrosative stress levels and damage, and mitochondria damage, damage to the nervous sytem, with or without infection(s)

Neurasthenia
The term  ‘Neurashtenia’  was used in the late 19th century to describe an illness similar to ME. Neurasthenia has never been defined with precision and biomarkers, and it is a clinical non entity. It is well established as a means to not bother diagnosing a patient properly and not carry out appropriate laboratory and medical tests.  And to neglect the patient. Neurasthenia  is a term which was replaced regularly by doctors who took the time and effort to properly investigate, diagnose and test an illness.

 This was the case when the name ‘Neuroasthenia’ was replaced during epidemics and clusters, notable replacements being ‘Epidemic  Neuromyasthenia’,  ‘Encephalitis’,  ‘Akureyri Disease’, 'Iceland disease', ‘atypical poliomyelitis’,  ‘poliomyelitis-like epidemic neuromyasthenia’, 'diencephalitis',  ‘Abortive Poliomyelitis’,  ‘Myalgic Encephalomyelitis’ from the 1920’s to the 1990’s. These were typical ME outbreaks. These various names describe a biological illness with underlying infections and biological dysfunctions and abnormalities.  ‘Neurasthenia’ was falsely applied to these illnesses in the past, and encouraged by some medical authorities, but it’s ineffectiveness and failure as a term, a name, a definition, a description was and still is clear for all to see.  Where the term ‘Neurasthenia’ was replaced during these epidemics, patients had a better chance of getting proper medical treatment. One should not describe physical, biological illnesses as psychiatric or psychological, but this basic rule of science and medicine has not fully been heeded in some quarters, even today. It is very clear that the use of the term ‘Neurasthenia’ is a means to dismiss patients, neglect patients, and give them a false and meaningless psychiatric diagnosis which totally ignores the underlying pathology, disease processes and biological dysfunctions.

Neurasthenia is a meaningless term, a clinical non entity, which should be removed from modern medical textbooks worldwide.


The Harmful Effects of CBT and GET in ME / CFS cases. The Inefficacy of CBT and GET.

There have been many research findings and clinical findings which show the harmful effects of CBT and GET and exertion in ME / CFS patients. In addition to this, the inefficacy of CBT and GET in terms of lack of full recovery, lack of return to normal function, lack of normal health (prior to illness), lack of return to sporting and other social activities, lack of return to full time employment or full time education or training has also been shown. This research is listed in the links below


Some Recent Press and Media Coverage

-'I've got the bones of a 100-year-old because I’ve been in bed for seven YEARS': 22-year-old with severe ME could break a rib by just sitting up too fast Daily Mail, Britain, December 26th 2013

The ME victim's diary of despair: 'My body is tired and my spirit is broken. I have had enough, I long to die' Daily Mail 2010

Man crippled by ME for 30 years killed himself using drugs recipe from suicide handbook Daily Mail 25 April 2014

ME drove my daughter to suicide. Daily Mail newspaper

Who am I? My History with ME/CFS. By Mary M. Schweitzer, Ph.D.

Dr. Montoya's successful treatments

Click on the follwing link to view letter addressed by Karina Hansen's parents to members of the Danish Parliament


References

1. ME Primer for Healthcare Professionals: based on Myalgic encephalomyelitis: International Consensus Criteria, 2011 and 2003

Lorusso L, Mikhaylova SV, et al. Immunological aspects of chronic fatigue syndrome. Autoimmun Rev 2009; 8: 287-91.

Regional distribution of fatiguing illnesses in the United States: a pilot study. Cynthia Bierl, Rosane Nisenbaum, David C Hoaglin, Bonnie Randall, Ann-Britt Jones, Elizabeth R Unger and William C Reeves. Population Health Metrics 2004, 2:1 

The economic impact of chronic fatigue syndrome in Georgia: direct and indirect costs. Lin JM, Resch SC, Brimmer DJ, Johnson A, Kennedy S, Burstein N, Simon CJ. Cost Eff Resour Alloc. 2011 Jan 21;9(1):1.



Structure of Causation and Continuation

(i) Can acute infections lead to chronic illness and infections, and other biological abnormalities ?

(ii) Chronic Infections & Chronic Immune system dysfunction with progression to Neuroinflammation and Neurological, Endocrine, Mitochondria, Vascular, Cardiac and GI dysfunctions and abnormalities

 

(i) Can acute infections lead to chronic illness and infections, and dyfunctional immune systems and other biological abnormalities ?

O'Connor et al. (2006) at the Centers for Disease Control and Prevention state . "Evidence now confirms that noncommunicable chronic diseases can stem from infectious agents. Furthermore, at least 13 of 39 recently described infectious agents induce chronic syndromes. Identifying the relationships can affect health across populations, creating opportunities to reduce the impact of chronic disease by preventing or treating infection.… infectious agents likely determine more cancers, immunemediated syndromes, neurodevelopmental disorders, and other chronic conditions than currently appreciated."
Science is continuing to uncover the impact of acute virus, mycoplasma and bacteria infections in the development of chronic illness. See Emerging infectious determinants of chronic diseases. O'Connor SM, Taylor CE, Hughes JM. Emerg Infect Dis. 2006 Jul;12(7):1051-7.



Source: Emerging infectious determinants of chronic diseases. O'Connor SM, Taylor CE, Hughes JM. Emerg Infect Dis. 2006 Jul;12(7):1051-7

"For example, fully 10% of people who suffered from E. coli food poisoning later developed a relatively infrequent life-threatening complication called hemolytic uremic syndrome (HUS) where their kidneys and other organs fail. (3) Approximately two-thirds of patients with Guillain-Barre syndrome, a suspected autoimmune syndrome, have a history of an antecedent respiratory tract or gastrointestinal infection. (4) Campylobacter infection is the most commonly identified precipitant of GBS and can be demonstrated in as many as 30 percent of cases. (5) Reactive arthritis (Reiter's syndrome) is another excellent example. Reactive arthritis is classically seen following infection with enteric pathogens such as Yersinia, Salmonella, Campylobacter and Shigella. (6) In a 2006 study, Alan S. Brown of Columbia University showed that prenatal infections such as rubella, influenza, and toxoplasmosis are all associated with higher incidence of schizophrenia. (7) Brown found a seven-fold increased risk of schizophrenia when mothers were exposed to influenza in the first trimester of gestation. One final example: a 2010 study concluded that cesarean delivery is associated with 1.8 times higher risk of celiac disease but not inflammatory bowel disease in children. (8)"

"A case-controlled study of residents of the Isle of Man found that 40 percent of people with sarcoidosis had been in contact with a person known to have the disease, compared with 1 to 2 percent of the control subjects.(12) Another study reported three cases of sarcoidosis among ten firefighters who apprenticed together.(13) A cluster of 13 cases of Parkinson's disease among a community of 592 people were reported in Israel, significantly more that would be expected by chance.(14) Research suggests that obesity is also an inflammatory disease caused by certain species of the Th1 pathogens. A study recently published in the New England Journal of Medicine found that a person's risk of becoming obese increases by 57% if they have a friend who becomes obese, and by 37% if their spouse becomes obese.(15) According to the researchers: "These clusters did not appear to be solely attributable to the selective formation of social ties among obese persons." "
Source: http://mpkb.org/home/pathogenesis/evidence_bacteria

Guillain-Barre syndrome
It is now well accepted by medical doctors and scientists worldwide (in 2016) that Guillain-Barre syndrome can be caused by viral infections or bacteria infections. This is confirmed by scientific research studies and clinical cases. This is an example of
(i) an acute disease causing a chronic disease, which is often misdiagnosed or not diagnosed
(ii) a disease with different causative factors. It is caused by a number of different viruses or bacteria. This undermines the theory of one disease caused by only one germ.
In many cases the common cold is the cause, but other infections such as Zika virus, Epstein Barr and Herpes family infections which go into the nervous system and brain cause many cases of Guillain-Barre. These factors are being neglected by most doctors and healthcare systems and patients are often left to linger for years with no diagnosis or a misdiagnosis.

Jang et al. (2009) at St. Jude Children's Research Hospital, USA, discovered that an H5N1 Bird Flu (strain A/VN/1203/1204) infection in mice causes severe loss of tyrosine-hydroxylase positive dopaminergic neurons 60 days after infection by provoking a destructive autoimmune response, thus suggesting the infection by certain strains of flu might increase the risk of Parkinson's disease in humans.
Source: Haeman, Jang; David Boltz; Katharine Sturm-Ramirez; Kennie R. Shepherd; Yun Jiao; Robert Webster; Richard J. Smeyne (2009-08-10). "Highly pathogenic H5N1 influenza virus can enter the central nervous system and induce neuroinflammation and neurodegeneration". Proceedings of the National Academy of Sciences 106 (33): 14063–8.

Research findings over many years have confirmed a link between the Herpes infections, and Lyme and other bacteria infections and the development of Alzheimer's disease, MS and other neurological illnesses.
Source: Alzheimers disease and Herpes infections & Bacteria infections
Source: Research findings in MS, Alzheimers disease , Parkinsons disease, SLE, RA, Sjogrens syndrome, etc.

Research by Fonseca et al. (2015) found that infections can lead to chronic immune system dysfunctions which can persist for long periods afrer an infection is cleared. And these immune dysfunctions can make a person more vulnerable to other infections and inflammatory illnesses, such as allergies over time.
Source: Fonseca DM, Hand TW, Han SJ, Gerner MY, Glatman Zaretsky A, Byrd AL, Harrison OJ, Ortiz AM, Quinones M, Trinchieri G, Brenchley JM, Brodsky IE, Germain RN, Randolph GJ, Belkaid Y. Microbiota-dependent sequelae of acute infection compromise tissue-specific immunityExternal Web Site Policy. Cell (2015).

The Dubbo Studies 
These detail the effects of chronic infection and a post-infectious dysfunctional immune system in ME & CFS which can continue for years.
Post-infective and chronic fatigue syndromes precipitated by viral and non-viral pathogens: prospective cohort study. Hickie I, Davenport T, Wakefield D, Vollmer-Conna U, Cameron B, Vernon SD, Reeves WC, Lloyd A; Dubbo Infection Outcomes Study Group. BMJ. 2006 Sep 16;333(7568):575. Epub 2006 Sep 1.
Cytokine polymorphisms have a synergistic effect on severity of the acute sickness response to infection. Vollmer-Conna U, Piraino BF, Cameron B, Davenport T, Hickie I, Wakefield D, Lloyd AR; Dubbo Infection Outcomes Study Group. Clin Infect Dis. 2008 Dec 1;47(11):1418-25. doi: 10.1086/592967. 

Infection(s), chronically activated Immune system and Neuroinflammation & Oxidative and Nitrosative stress and damage in Neurological illnesses
Activated immune pathways and inflammatory cytokines and inflammatory markers, and neuroinflammation, and high oxidative and nitrosative stress levels and damage, and mitochondria damage, damage to the nervous system, with or without infection(s) has been found in neurodegenerative diseases such as Parkinsons, Alzheimers, MS and many others. This causes extreme fatigue and tiredness. This is also found in autoimmune diseases. And they are also found in ME and CFS, a neurological illness according to WHO, with immune system dysfunctions.


The Complexity of Diagnosing Chronic Complex Illnesses involving Stealth Infections and Multiple Biological Dysfunctions

The following presentation was made to the Belgian Parliament in June 2014 by Dr. Richard Horowitz, an American medical doctor who has treated over 12,000 patients with Chronic Lyme, CFS, ME, Fibromyalgia and other infectious diseases
https://www.youtube.com/watch?v=JSx3KdFaupA&t=8m40s


What is ME and CFS ? Multiple Paths leading into ME and CFS

Causes of Heterogenity, Excessive Subgroups & Phenotypes and inability to find a Universal Biomarker, and the Conflicting Test Results and Treatment Outcomes


Genetic Studies

Some genetic studies support the role of infections(s) and immune dysfunctions in ME.


Chronic Infections and Reactivated latent viruses - A. Melvin Ramsay M.D

"Although the aetiological factor or factors have yet to be established, there are good grounds for postulating that persistent virus infection could be responsible. It is fully accepted that viruses such as herpes simplex and varicella-zoster remain in the tissues from the time of the initial invasion and can be isolated from nerve ganglia post-mortem; to these may be added measles virus, the persistence of which is responsible for subacute sclerosing panencephalitis that may appear several years after the attack and there is a considerable body of circumstantial evidence associating the virus with multiple sclerosis. There should surely be no difficulty in considering the possibility that other viruses may also persist in the tissues. In recent years routine antibody tests on patients suffering from myalgic encephalomyelitis have shown raised titres to Cocksackie B Group viruses. It is fully established that these viruses are the aetiological agents of 'Epidemic Myalgia' or 'Bornholm's Disease' and that, together with ECHO viruses, they comprise the commonest known virus invaders of the central nervous system. This must not be taken to imply that Cocksackie viruses are the sole agents of myalgic encephalo- myelitis since any generalised virus infection may be followed by a period of post-viral debility. Indeed, the particular invading microbial agent is probably not the most important factor. Recent work suggests that the key to the problem is likely to be found in the abnormal immunological response of the patient to the organism. "
Source: MYALGIC ENCEPHALOMYELITIS : A Baffling Syndrome With a Tragic Aftermath. By A. Melvin Ramsay M.D., Hon Consultant Physician, Infectious Diseases Dept, Royal Free Hospital. [Published 1986]

The scientific research findings of Dr. Garth Nicolson show that co-infections are common in those people with chronic illness. We have provided listings of his research papers on this web site. In her speech at the International Congress of Autoimmunity, Amy Proal stated that of the Marshall Protocol subjects with Hashimoto's thyroiditis who participated in a survey, only 8% with Hashimoto's had Hashimoto's alone. The Hashimoto's patients had at least one, sometimes several comorbidities or co-infections. The same has been found in other patients with autoimmune and chronic illnesses, while they were receiving Marshal Protocol treatment.

The Marshall Protocol was devised by Professor Trevor Marshall. It is based on the premise that bacteria, fungi and viruses interact to cause chronic inflammatory illnesses.  This includes MS, autoimmune illnesses, ME, neurological illnesses,  Lyme disease, arthritis, rheumatism.  Most of these illnesses involve disrupted and dysfunctional immune systems and chronic inflammatory conditions.  Many of these infections are not picked up in standard tests, but they can inflict chronic inflammation and damage over time.   A recent research paper at http://mpkb.org/home/publications/proal_autoimmunity_reviews_2009  explores this in more detail.  The NIH has estimated that 90% of the cells in Homo sapiens are microbial and not human in origin. Some of these microbes create metabolites that interfere with the expression of genes associated with autoimmune disease.

Dr. Marshall has found that a dysfunctional VDR lies at the root of many cases of ME and CFS and other autoimmune and neurological illnesses.  It leaves a person vulnerable to attack by viruses, bacteria and fungi and causes a deterioration in the patient over time. The following video lecture provides a good overview of the relationship between ME / CFS and chronic infections.
https://www.youtube.com/watch?feature=player_embedded&v=2IMdAV6SIMU


(ii) Chronic Infections & Chronic Immune system dysfunction with progression to Neuroinflammation and Neurological, Endocrine, Mitochondria, Vascular, Cardiac and GI dysfunctions and abnormalities

One or more pathogens are suspected of being triggering agents for the illness. Cumulative pathogen load is important over time prior to ME onset and after ME onset. Immune system dysfunction is related to pathogen infection and pathogen load over time. Most of these viruses, mycoplasmas enteroviruses, chlamydia and other pathogens are not being detected in standard or outdated tests. Many doctors and research trials have failed to undertake intensive tests of spinal fluid and inflamed samples from dorsal root ganglia tissues, basal ganglia, brain stem, vagus nerve, spinal cord, cervical and lumbar nerve roots and peripheral nerves, and sites of brain lesions, intestinal tissues and muscle tissues to detect these pathogens. Many patients have been told they have no infection, when they actually have an infection which cannot be detected with outdated diagnostic equipment.

The immune system dysfunctions and abnormalities in ME patients makes them more susceptible to various infections. The acquired infection(s) will depend on one's geographical location and exposures, and one's genetic status and immune system status. Some of the following pathogens have been consistently found in ME patients:

Viruses include: Reactivated (latent) EBV virus, particularly in nervous system, glands and organs, HHV6a virus, Herpes family viruses 1-8, Parvovirus B-19, CMV, Coxsackie viruses, Enteroviruses, Ross river virus, Q fever virus, Stealth virus, JHK virus,  Parainfluenza Virus-5 (PIV-5), Paramyxovirus and measles viruses of the  Paramyxoviridae family, Cryptovirus, Borna virus, HTLV family viruses, HGRV virus in spinal fluids, nerve tissues, blood, brain, intestines, and muscles. Retroviruses are important, as Retrovirus sequences were found in 85% of ME cases, and Anellovirus found in 75% of ME cases in research conducted by Dr. Hornig and Dr. Lipkin in Columbia University in September 2013. Most of these viruses listed here would include chronic, low level, sub-acute infections which inflict damage and immune activation, but which may not show up in standard or outdated tests.
Reactivated latent viruses include HERV-K18, Varicella-Zoster virus, Herpes family viruses 1-8, measles viruses of the  Paramyxoviridae family. Some viral infections can reactivate latent viruses and undermine immune system functions.

Mycoplasma: M. fermentans, M. penumoniae, M. hominis, M. penetrans, M. pirum,  M. incognito. in intestines, spinal fluids, blood, brain, nerve tissues, muscles. These mycoplasmas would include chronic, low level, sub-acute infections which inflict damage and immune activation, but which may not show up in standard or outdated tests.
Bacteria: Chronic Lyme disease, Ehrlichia, Bartonella, Brucella, Rickettsia, Chlamydia pneumonia, Staphylococcus spp. (live blood analysis), and Bacteria, including Microbiota of bacteria which include L-form, biofilm, and intracellular bacterial forms in spinal fluids, intestines, blood, brain, nerve tissues, muscles. Intestinal overgrowth of Gram positive D/L lactate-producing bacteria which are known to produce H2S (hydrogen sulfide) in the presence of certain heavy metals as a survival defense mechanism (Dr. Kenny De Meirleir). These bacteria would include chronic, low level, sub-acute infections which inflict damage and immune activation, but which may not show up in standard or outdated tests.
Parasite: Cryptostrongylus pulmoni, Babesia, Candida, Giardia lamblia, Aspergillus Niger
Molds, Bacteria and Mycotoxins in water damaged buildings: Stachybotrys family of molds, Cladosporium, Penicillium, Alternaria, Aspergillus, mycobacteria, Actinomycetes, Lipopolysaccharides (LPS), Microbial Volatile Organic Compounds (VOCs), Hemolysins. These can cause chronic inflammatory immune response and immune dysfunction over time.

These infections may be causative, opportunistic or a co-factor in the illness.

What is ME ? Multiple Paths leading into ME
Causes of Heterogenity, Excessive Subgroups & Phenotypes and inability to find a Universal Biomarker, and the Conflicting Test Results and Treatment Outcomes

A coroner's report of ME patient Sophia Mirza revealed that 4 out of 5 dorsal root ganglia were abnormal and showed disease. The coroner had not been able to find exactly what had caused this but the result was dorsal root ganglionitis – an inflammation. This suggests an infection of this area. An MRI scan or MRS scan or samples of this area would have revealed abnormalities, infections and inflammation while she was alive, but unfortunately this was never done. She was refused these tests by some doctors. These neurological abnormalities and extensive damage to the brain and nervous system were confirmed in another autopsy of a dead ME / CFS patient in 2017.

'Chronic fatigue syndrome (CFS) is characterized as a persistent, debilitating complex disorder of unknown etiology, whereby patients suffer from extreme fatigue, which often presents with symptoms that include chronic pain, depression, weakness, mood disturbances, and neuropsychological impairment. In this mini review and case report, we address central nervous system (CNS) involvement of CFS and present neuropathological autopsy findings from a patient who died with a prior diagnosis of CFS. Among the most remarkable pathological features of the case are focal areas of white matter loss, neurite beading, and neuritic pathology of axons in the white matter with axonal spheroids. Atypical neurons displaying aberrant sprouting processes in response to injury are observed throughout cortical gray and white matter. Abundant amyloid deposits identical to AD plaques with accompanying intracellular granular structures are observed as well. Neurofibrillary tangles are also present in the white matter of the frontal cortex, thalamus and basal ganglia. Taken together, these neuropathological findings warrant further studies into CNS disease associated with CFS.'
CNS findings in chronic fatigue syndrome and a neuropathological case report. Kimberly Ferrero, Mitchell Silver, Alan Cocchetto, Eliezer Masliah, Dianne Langford DOI: 10.1136/jim-2016-000390 Published 6 April 2017

There is a lot of evidence of viral and bacteria infections in ME / CFS, see Scientific Evidence and these may account for the damage to the brain and nervous system.

Recent ME subgroup recoveries from use of the medical drug Rituximab which is used for autoimmune illnesses and Cancers, strongly suggests autoimmunity involving B-cells and / or infection of B cells or B cell generation mechanisms as the key component in the illness, in addition to other immune system dysfunctions. Research shows close relationship between certain infections and the development of autoimmunity.

The current scientific research and clinical findings support the following conclusions:

Initiation of illness

In the diagram below, the virus or other pathogen may be
(a)
exploiting an existing weakness in the immune system and/or genetic profile of the person brought about by several environmental and genetic factors
OR
(b)
creating certain weaknesses in the immune system and / or genes, and these weaknesses persist over time and contribute to other immune system weaknesses and to opportunistic infections, and to further genetic effects, and a domino effect, affecting other body systems over time.
The end result is a chronic illness characterised by inflammation, infection, mitochondria defects and low energy, and neurological, cardiac, and HPA axis abnormalities, and continuing damage to cells, tissues and nerves, affecting many body parts, and causing deterioration of the patient over time.

- The Dubbo studies and other research findings mentioned above, and the scientific findings itemised in the Scientific Evidence section verify and corroborate this

- Kerr et al provide evidence of other triggers of (ME)CFS which include Parvovirus; C. pneumoniae; C. burnetti; toxin exposure and vaccination including MMR, pneumovax, influenza, hepatitis B, tetanus, typhoid and poliovirus (LD Devanur,  JR Kerr. Journal of Clinical Virology 2006: 37(3):139-150).
And the findings of medical doctors, over many years, also corroborate this - see Dr. Montoya's successful treatments

- Dr. John Richardson, a medical doctor based in Newcastle in England treated ME patients from many parts of Britain for over 40 years. He developed an expertise in diagnosing the illness, and became one of the world's foremost experts in ME. He even used autopsy results from dead patients to investigate the illness. He found that Enteroviruses and toxins played a major role in ME, and that this led to immune dysfunction, neurological abnormalities, endocrine dysfunction, and over time to increased risk of cardiac failure, cancers, carcinomas, and other organ failure. He wrote a book about his medical experiences called Enteroviral and Toxin Mediated Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. The part played by undiagnosed viruses and immune dysfunctions continues to be important in the illness.

- "The outbreak in Iceland was important, and provided some vital clues about the illness and the role of Enteroviruses.
"However, children in epidemic Neuromyasthenia areas responded to poliomyelitis vaccination with higher antibody titres than in other areas not affected by the poliomyelitis epidemic, as if these children had already been exposed to an agent immunologically similar to poliomyelitis virus (Sigurdsson, Gudnad6ttir Petursson, 1958). Thus, the agent responsible for epidemic Neuromyasthenia would appear to be able to inhibit the pathological effects of poliomyelitis infection. When an American airman was affected in the 1955 epidemic and returned home, a similar secondary epidemic occurred in Pittsfield, Massachusetts, U.S.A. (Hart, 1969: Henderson and Shelokov, 1959)."
Many outbreaks of ME or epidemic Neuromyasthenia worldwide followed an outbreak of polio virus.
Parish JG (1978), Early outbreaks of 'epidemic neuromyasthenia', Postgraduate Medical Journal, Nov;54(637):711-7, PMID: 370810.

- The ME or epidemic Neuromyasthenia outbreak at Rockville, U.S.A. (Shelokov et al., 1957), was associated with the isolation, from a number of the patients, of Bethesda-Ballerup paracolon organisms which appear to have triggered off the disease in the same manners as infection with poliomyelitis virus pre-cipitated other epidemics. 
Parish JG (1978), Early outbreaks of 'epidemic neuromyasthenia', Postgraduate Medical Journal, Nov;54(637):711-7, PMID: 370810.

- Research by Dr. Acheson shows that ME or epidemic Neuromyasthenia outbreaks occured during or after polio outbreaks or other viral outbreaks. This points to various viral causes of ME.
The Clinical Syndrome Variously Called Benign Myalgic Encephalomyelitis, Iceland Disease and Epidemic Neuromyasthenia. Dr. Acheson, American Journal of Medicine, 1959.

- Lake Tahoe outbreak
The Harvard-led research team found abnormal MRI brain scans, significant alterations in white blood cells counts and functioning, and signs of active infection with a recently discovered pathogen, HHV-6a. The illness was likely a “chronic, immunologically mediated inflammatory process of the central nervous system.”
Buchwald, D., Cheney, P., Peterson, D., Henry, B., Wormsley, S., Geiger, A., Ablashi, D., Komaroff, D.etc. 1992. A chronic illness characterized by fatigue, neurologic and immunologic disorders, and active Human Herpesvirus Type 6 Infection. Annals of Internal Medicine 1116: 103-13. (The seminal scientific research paper on the Lake Tahoe epidemic in the USA in the mid 1980's and the origin of the term CFS)

This is corroborated by the medical findings presented by Dr. Cheney, Dr. Peterson, Dr. Holmes, Dr. Komaroff, and others to the CDC and Federal health bodies and scientific journals during and after the Lake Tahoe outbreak which confirmed a rapidly spreading infectious disease with a short incubation period of one week or less which progressed to a chronic illness within 6 months. This incubation period narrows down the causative agent for the illness. High numbers of patients had HHV6a (then called HBLV), some had EBV, including reactivated EBV, some had CMV infection, some had serious Herpes simplex infections and some had measles infection. A significant number had several infections at the same time, including re-activated latent viruses.

All of these particular infections have an incubation period of greater than one week. The exception to this being latent versions of these viruses which can be reactivated within a day or a few days, and certainly less than one week. Some Enteroviruses have an incubation period of 1 week or less. Infection by bacteria, including brucella and other pathogens were also found in some patients, these typically have incubation periods of less than one week. Certain unusual immune system abnormalities and dysfunctions were found which undermined the body's ability to fight viruses and pathogens ; these may have been caused by the causative infectious agent.

The diagnosis of HHV6a was undermined by the fact that it was newly discovered and most doctors did not test for it and by outdated diagnostic technologies at the time which could not test for it. Click here on the following link to view some medical findings from the Lake Tahoe epidemic.

- Enteroviruses, indicated in most ME epidemics throughout history, were not tested for in the Lake Tahoe epidemic. Enteroviruses have been associated with ME since the 1930's. Names such as 'Epidemic  Neuromyasthenia’,  ‘Encephalitis’,  ‘Akureyri Disease’, ‘atypical poliomyelitis’, 'Iceland disease',  ‘poliomyelitis-like epidemic neuromyasthenia’, 'diencephalitis',  'diencephalitis', ‘Abortive Poliomyelitis’ were used to describe the illness prior to the term ‘Myalgic Encephalomyelitis’ being created by Dr. Melvin Ramsey in 1956. Enteroviruses were implicated in most epidemics from the 1930's to the present day.
" Primary M.E. is always an acute onset illness. Doctors A. Gilliam, A. Melvin Ramsay and Elizabeth Dowsett (who assisted in much of his later work,) John Richardson of Newcastle-upon-Tyne, W.H. Lyle, Elizabeth Bell of Ruckhill Hospital, James Mowbray of St Mary's, and Peter Behan all believed that the majority of primary M.E. patients fell ill following exposure to an enterovirus. (Poliovirus, ECHO, Coxsackie and the numbered viruses are the significant viruses in this group, but there are other enteroviruses that exist that have been discovered in the past few decades that do not appear in any textbook that I have perused.) I share this belief that enteroviruses are a major cause. "
Source: http://www.nightingale.ca/documents/Nightingale_ME_Definition_en.pdf

- Immune system abnormalities identified in Lake Tahoe epidemic - Low natural killer cell numbers and lowered cytotoxicity, B cell abnormalities, high levels of inflammatory cytokines, particularly IL-2. Drs. Komarroff, Cheney and Peterson believed a pathogen was involved in natural killer cell depletion, most likely a virus. These findings were never fully followed up by CDC and NIH and other research bodies in other countries since 1991
In the book Osler's Web: Inside the Labyrinth of the Chronic Fatigue Syndrome Epidemic by Hillary Johnson medical doctors in the USA found an unusually high number of B cell lymphomas in ME / CFS patients. Special scientific tests showed that these B-cell Lymphomas in ME patients were unusual types, not seen before. The researchers found B-cell deficiency in all patients, and a positive result on the kappa/lambda assay for a majority of these patients. After studying samples from approximately fifty patients, Wormsley estimated that the rate of clonal excess abnormality in the CFS patients from Nevada was at least 25 percent ('Oslers Web, by Hillary Johnson, Penguin Books 1997, page 94). This is significant as kappa/lambda light chains are the result of abnormalities within the bone marrow B-cell lineage. This has direct on B-cells and overall immunity, and susceptibility to Cancers. Recent scientific studies show that the incidence rate of non-Hodgkin's lymphoma is 0.02% in the United States, yet nearly 5% of CFS patients develop the disease. This is a significant risk factor.

- During the Lake Tahoe outbreak, some patients had pre-existing chronic inflammatory immune response to mycotoxins and molds prior to developing full ME / CFS. Doctor's and researchers findings at the time confirmed most patients had severe allergies and some had sinusitis prior to the epidemic. These mycotoxins and molds play a part in instigating immune system dysfunctions and weaknesses, and scientific research now shows this to be the case. This may have caused patients to become more susceptible to viral and other infections during the Lake Tahoe epidemic. A weakened immune system always makes one more susceptible to infections, and this is paticularly true if this weakness exists over a long period of time. Interestingly some patients improved significantly and even recovered after they left the buildings containing molds and mycotoxins and got treatment for the viral and other infections. The link between chronic inflammatory immune response to mycotoxins and molds and increased susceptibility to viral infections and other infections is being researched by Dr. Shoemaker in the USA and by other scientific researchers.

- The virus may be incubating in and infecting the B-cells, thus initiating a viral infection, chronic immune system activation and dysfunctions, and autoimmunity simultaneously.

- The virus / pathogen may also be infecting the mitochondria or injuring it or blocking it and interrupting the krebs cycle and this is having a domino effect on the immune system and it's functions and signalling systems.

- The virus / pathogen may be chronically activating both inflammatory cytokines and microglia, creating a long-term inflammatory illness with significant pain and biological abnormalities.

- Blocks in the methylation cycle and in methylation can cause immune system abnormalities, including re-activation of latent viruses, thyroid and endocrine abnormalities, excess inflammation, antioxidant deficiencies, high homocysteine levels, arteriosclerosis and cardiac abnormalities, fatty liver, increased Cancer risk, neurotransmitter abnormalities and mood disorders, IBS, detoxification deficiency, multiple chemical sensitivity, cell growth and maintenance abnormalities. All of these are commonly found in most ME and CFS patients.

- Chronic mercury and nickel poisoning are consistently found in many ME patients. These heavy metals are destructive to the mitochondria, the immune system, the glands and HPA axis, the brain and the nervous system.

Progression to chronic state

- Progression to chronic illness 6 -12 months. Several body systems are adversely affected by this. There are immune system dysfunctions, increased oxidative and nitrosative stress, neuroinflammation, damaged mitochondria, and damage to the brain and nervous system, the glands and HPA axis, the heart, the blood vessels, the muscles, and the liver. All of these are inter-related body systems have feedback loops between them, contributing to a perpetuation of the illness, more dysfunctions and a worsening of the illness over time. Subgroups of patients depending on genetics, environment, geographical location, exposures to pathogens, vaccine reactions and toxins, length of time suffering illness and accumulation of biological dysfunctions and abnormalities, etc.

- The course of the illness depends on the infection(s) acquired, toxins load, mold allergy and immune dysfunctions present and developed as the patient's condition worsens over time.
Causes of Heterogenity, Excessive Subgroups & Phenotypes and inability to find a Universal Biomarker, and the Conflicting Test Results and Treatment Outcomes

- The chronic state is usually arrived at through neglect of the patient, misdiagnosis, inadequte testing, psychiatric nonsense, out-dated diagnostic equipment, doctor's not knowing about ME / CFS, old, out-dated procedures, etc. and patients are left with chronic infections and several biological dysfunctions and abnormalities with an increased risk of premature death. This neglect and misdiagnosis imposes a huge burden on the patient and his / her family, and on the health system and on the government and taxpayers.

- Mitochondria Analysis & Cardiac Analysis

Source: Dr. Paul Cheney, The Cheney Clinic, USA.

Source: Dr. Paul Cheney, The Cheney Clinic, USA.



Source: Dr. Sarah Myhill. Myhill Medical Clinic, Wales.

Cardiomyopathy arising from mitochondria dysfunction, oxidative stress and infections



Source: Peckerman et al. 2003

- The virus / other pathogens and immune dysfunctions are reactivating latent endogenuous viruses with super antigens in some cases, which damage immune system function. The HERV viruses are implicated in this illness, as they are in other illnesses such as MS, AIDS, Rheumatoid arthritis. The herpes virus family 1-8 are also have latency states which become activated in some ME patients. Methylation cycle blocks and methylation failure can seriously undermine and weaken immune system function to the point that latent viruses can become active again.

- The virus / pathogen may be chronically activating both inflammatory cytokines and microglia and astrocytes, creating a long-term inflammatory illness with significant pain and biological abnormalities.

- Infection(s), chronically activated Immune system and Neuroinflammation & Oxidative and Nitrosative stress and damage in Neurological illnesses
Activated immune pathways and inflammatory cytokines and inflammatory markers, and neuroinflammation, and high oxidative and nitrosative stress levels and damage, and mitochondria damage, damage to the nervous system, with or without infection(s) has been found in neurodegenerative diseases such as Parkinsons, Alzheimers, MS and many others. This causes extreme fatigue and tiredness. This is also found in autoimmune diseases. And they are also found in ME and CFS, a neurological illness according to WHO, with immune system dysfunctions.

For the patient, there is immune system dysfunction and autoimmunity, chronic infection(s), and central nervous system and ANS dysfunction and increased Cancer risk and increased heart attack risk as an outcome. Other pathogens can then ruthlessly exploit these weaknesses in the immune system and body, explaining the other infections and re-activation of latent viruses.

In her lecture in November 2009 at the University of Miami, Professor Nancy Klimas stated that most of the research in the USA and internationally found that the viruses found in ME all have several things in common:  they infect the immune system and the neurological system; they are capable of causing latent infections and they can reactivate under certain conditions.

Click on the following links for diagrams depicting the chronic state of ME / CFS


Chronic Immune Dysfunction and Inflammatory State, Infection(s), Neurological, Endocrine, Mitochondria, and Oxidative Stress Cycles


Effects of Exercise on Mitochondria, Heart, Immune system, and Nervous System


Causes of Heterogenity, Excessive Subgroups & Phenotypes and inability to find a Universal Biomarker, and the Conflicting Test Results and Treatment Outcomes

Newly discovered Viruses involved in ME
Scientific research points towards immune system damage caused by a virus or other pathogen or toxin which results in acquired immune weaknesses and dysfunctions, including chronic activation, which make patients more susceptible to viral infections and other infections. Research is consistently showing us chronic HHV-6a virus infection of the brain, brain stem, spine and nervous system and muscles and other body systems in 30% - 50% of ME patients  -  see research into HHV-6a virus (in.pdf format). HHV-6a virus also attacks the immune system and can keep it in a permanently weakened state. The HHV-6a virus is ‘neurotropic’ meaning it prefers to live in brain tissue, spinal fluids and in nerve tissue, and is not detected in routine blood tests. There is no test for this in Ireland. This is very important as new research is showing nervous system dysfunction in most ME patients, and this is being confirmed by genetic studies. In particular, dysfunction and inflammation of the dorsal root ganglia and other peripheral ganglia in the nervous system and the brain stem is known to be a factor in ME. HHV-6a virus may be infecting these sites in the body in ME, thus leading to several domino effects and resultant abnormalities and dysfunctions. The books America's Biggest Cover-Up: 50 More Things Everyone Should Know About The Chronic Fatigue Syndrome Epidemic And Its Link To AIDS by Neenyah Ostrom and The Virus Within By Nicholas Regush explore the role of HHV-6a virus in ME in more depth. These two books provide fascinating reading.

Research now shows that HHV6a virus is also involved in AIDS and Multiple Sclerosis (MS). This finding is very serious and warrants further investigation and research. This is investigated in more depth in our Scientific Evidence section The above abnormalities help explain the severe exhaustion, muscle pains, exercise intolerance, physical weakness, loss of memory, mental confusion, infections, lymph swelling and other symptoms found in ME . It is widely believed that a breakdown in the immune system is the root cause of ME , and that infections may be causative, a co-factor or opportunistic in this illness. Recent research is slowly unravelling the root causes of ME   -  click here for the main research priorities

Dr. John Chia in the USA has found enteroviral infections in a majority of ME patients. This confirms earlier findings from the 1950's, 1960's and 1970's concerning enteroviruses. These enteroviruses live in nerve tissues, the brain and nervous system, in muscles and in the intestines and cause significant damage and disability to a person over time. His scientific and clinical findings strongly suggest that many ME patients have entervirus infections and in some cases multiple viral infections (including HHV6a, CMV, Epstein Barr, enterovirus etc.), and that enteroviruses play a key role in the pathology of ME. You can view his findings by clicking here.

Retrovirus sequences have been found in 85% of ME cases, and Anellovirus found in 75% of ME cases in research conducted by Dr. Hornig and Dr. Lipkin in Autumn 2013, but this will require further analysis.

New scientific findings in the USA show that a significant percentage of ME patients are or were infected by Parainfluenza Virus-5 (PIV-5). This particular virus targets and degrades the STAT1 protein in the immune system, and this in turn leads to immune dysfunction. The destruction of STAT1 protein is one of the main features of ME, in addition to RnaseL abnormalities, PKR abnormalities, p53 protein abnormalities and Actin abnormalities. There is continuing scientific research to establish if this virus is causative, opportunistic or a co-factor in the illness. This research is being led by the National CFIDS Foundation in the USA which is continuing to fund and back excellent scientific research into ME. The Department of Homeland Security in the USA has also kindly assisted in this research and made some significant progress in terms of diagnosis and treatments. More information about these viruses can be found by clicking here.

Dr. Huber of Tufts University in the USA is carrying out research to determine if viral infections are leading to the reactivation of latent endogenous viruses such as HERV-K18 in ME patients. This is important as HERV-K18 has a super antigen which can cause the immune system to become over-activated and dysfunctional. Over time this can lead to a weakened immune system which is both activated and dysfunctional, and not capable of combatting other infections, and this is what we see in ME . This research will determine if this is what is occurring in ME and it is due to be published in 2013. Dr. De Meirleir and other researchers completed a ground breaking new study into HERV viruses and ME in Spring 2013. This strongly suggests HERV infection in the intestines and is detailed in the following paper Plasmacytoid Dendritic Cells in the Duodenum of Individuals Diagnosed with Myalgic Encephalomyelitis Are Uniquely Immunoreactive to Antibodies to Human Endogenous Retroviral Proteins. De Meirleir et al. in vivo27: 177-188 (2013). The re-activation of dormant endogenous viruses which are part of the human genome is a very recent and unexpected scientific finding and may explain the autoimmune aspects of ME and other illnesses. Research is ongoing into this.

Research from Australia shows that other less well known viruses such Ross river virus and Q fever virus may initiate ME. In addition, Epstein Barr virus was also examined in this study. (Peripheral blood gene expression in postinfective fatigue syndrome following from three different triggering infections.Galbraith S, Cameron B, Li H, Lau D, Vollmer-Conna U, Lloyd AR.. J Infect Dis. 2011 Nov 15;204(10):1632-40.). This supports the fact that several viruses are capable of causing ME and they can also act as a co-factor and /or opportunistic infection in the illness over time. They may also weaken immunity so as to reactivate latent viruses. This is the subject of ongoing scientific research in the context of pathogen / toxin subgroups.

Dr. John Martin of the Center for Complex Infectious Diseases has produced some research which suggests the involvement of stealth viruses in ME. You can read more about this at http://www.ccid.org/about.htm. It is a well accepted fact that there are many viruses and other pathogens not yet discovered by the medical and scientific community. The activation of the 2-5a synthetase / RnaseL anti-viral pathway in most ME patients suggests the involvement of viruses - discovered, partially discovered or recognised and undiscovered viruses. This is the subject of continuing scientific investigation and validation. It is important to re-state that viruses may be causative, opportunistic or a co-factor in this illness.

On the subect of chronic, hard to treat infections, and opportunistic infections, new research in 2014 has revealed that bacteria and other pathogens have evolved to use a protein called 'Protein M' to block all antibodies produced by the human immune system. This makes humans more vulnerable to acute and chronic infections and can provide wrong antibody readings in tests. This remarkable discovery by scientists at the Scripps Research Institute in 2014 sheds new light on chronic bacteria infections in humans. As many ME patients have chronic infections, this information is important. Research is ongoing to uncover the part played by Protein M in chronic infections and chronic illnesses. Other protein markers used by pathogens are also being investigated.
See information on this at http://www.scripps.edu/news/press/2014/20140206lerner.html

Rituximab, B-cell abnormalities & Viral induced Autoimmunity & Cancers
The scientific findings show that B-cell abnormalities play a significant role in autoimmunity in ME, and the success of the drug Rituximab confirms these findings. The scientific research of Fluge and Mella in Norway show that depleting B-cells through Rituximab brings about recoveries in two thirds of patients. Yet this takes several months to achieve. Once Rituximab is withdrawn, the patients become ill again after a few months, as B-cell numbers increase. Viruses / mycoplasmas may be hiding in B-cells so as to infect patients and/or increasing B-cell production for infection purposes, indirectly causing both an autoimmune response and an ongoing infection. Dr. Martin Lerner (Michigan, USA) believes that anti-virals kill the viruses, but do not hit the B-cells which incubate the virus(es) and that Rituximab hits the B-cells, but has little effect on the viruses. This would explain why Rituximab improves ME patients after a few months, but when Rituximab is stopped, the patients deteriorate, as (infected) B cell populations increase again. Dr. Michael Pender in his paper CD8+ T-Cell Deficiency, Epstein-Barr Virus Infection, Vitamin D Deficiency, and Steps to Autoimmunity: A Unifying Hypothesis. Pender MP. Autoimmune Dis. 2012;2012:189096. postulates that EBV virus is capable of living inside B cells and using the machinery of these cells to replicate itself, and cause continuing infection, autoimmunity and immune dysfunction which could last for years and decades. He also states that reduced cytotoxic T cell function plays a key role in this, allowing EBV infection of B cells and other cells to continue. This is explored further in the following papers Could the Epstein-Barr Virus – Autoimmunity Hypothesis Help Explain Chronic Fatigue Syndrome ? and EBV I: A Deficient Immune Response, Increased Levels of Epstein-Barr Virus Opens Up EBV Question in Chronic Fatigue Syndrome Again. An excellent scientific paper produced by scientific researchers in Germany in 2014 shows the importance of chronic EBV infection, including persistent reactivation of latent EBV combined with a defective immune system. This plays a major role in ME (Deficient EBV-specific B- and T-cell response in patients with chronic fatigue syndrome. Loebel M, Strohschein K, Giannini C, Koelsch U, Bauer S, Doebis C, Thomas S, Unterwalder N, von Baehr V, Reinke P, Knops M, Hanitsch LG, Meisel C, Volk HD, Scheibenbogen. Scientific analysis and discussion on http://simmaronresearch.com/2014/03/1591/ )

Scientific research in 2012 and 2013, by Dr. Bansal et al. in Britain shows unusual B cell abnormalities in ME patients, which suggest autoimmune factors.

' patients had greater numbers of naive B cells as a percentage of lymphocytes: 6·3 versus 3·9% in HC (P = 0·034), greater numbers of naive B cells as a percentage of B cells: 65 versus 47% in controls (P = 0·003), greater numbers of transitional B cells: 1·8 versus 0·8% in controls (P = 0·025) and reduced numbers of plasmablasts: 0·5 versus 0·9% in controls (P = 0·013). While the cause of these changes is unclear, we speculate whether they may suggest a subtle tendency to autoimmunity.'

(Bansal et al., (2013), Altered functional B cell subset populations in patients with chronic fatigue syndrome compared to healthy controls. Clinical & Experimental Immunology, 172: 73–80.)

This ties in to important scientific findings in the book Osler's Web: Inside the Labyrinth of the Chronic Fatigue Syndrome Epidemic by Hillary Johnson where medical doctors in the USA found an unusually high number of B cell lymphomas in ME patients. Special scientific tests showed that these B-cell Lymphomas in ME patients were unusual types, not seen before. The researchers also found B-cell deficiency in all patients, and a positive result on the kappa/lambda assay for a majority of these patients. This is significant as kappa/lambda light chains are the result of abnormalities within the bone marrow B-cell lineage. This has direct on B-cells and overall immunity, and susceptibility to Cancers.

Recent scientific studies show that the incidence rate of non-Hodgkin's lymphoma is 0.02% in the United States, yet nearly 5% of ME patients develop the disease. This is a significant risk factor. Furthermore, the increase in NF-Kb levels consistently found in most ME patients shows both an increase in inflammation and an increase in general Cancer risk. The National Cancer Institute, USA, has recently confirmed that there is a higher risk of these types of Cancers in ME patients ( Chang, C. M., Warren, J. L. and Engels, E. A. (2012), Chronic fatigue syndrome and subsequent risk of cancer among elderly US adults. Cancer, 118: 5929–5936. doi: 10.1002/cncr.27612 ). Among non-Hodgkin lymphoma subtypes, ME was associated with diffuse large B cell lymphoma and marginal zone lymphoma and B cell NHL not otherwise specified. They concluded that infection and chronic immune system dysfunction may play a role. Certainly the defects in B cells and defects in Natural Killer cell functions and numbers in addition to certain viral infections, and high levels of oxidative and nitrosative stress leaves many ME patients vulnerable to Cancers. Interestingly, a relationship between EBV infection and B cell Lymphomas has recently been found by researchers, and as both are found in ME patients, this may shed more light on ME and it's risk for factor for Cancer. The research paper can be viewed here at :
Snow AL, Lambert SL, Natkunam Y, Esquivel CO, Krams SM, Martinez OM (2006), EBV can protect latently infected B cell lymphomas from death receptor-induced apoptosis , J Immunol, Sep 1;177(5):3283-93.

EBV, especially chonric EBV infection is implicated in B cell lymhomas, B cell abnormalities, immune system dysfunctions, Cancers and liver failures and ME/CFS.
- Characterization and treatment of chronic active Epstein-Barr virus disease: a 28-year experience in the United States
- Optimal Treatment for Chronic Active Epstein-Barr Virus Disease

HHV-6a virus which has been consistently found in high pecentages of ME patients has been found to be associated with Hodgkin's lymphoma, acute lymphocytic leukemia, African Burkitts lymphoma, and sarcoidosis, as well as AIDS and Chronic Fatigue Syndrome. Lusso, P. et al.; "In Vitro Cellular Tropism of Human B-Lymphotropic Virus(Human Herpesvirus-6)"; Journal of Experimental Medicine 167:1659, May 1988). HHV-6a also destroys the B-cells of the immune system. This has been found in research carried out by Dr. Robert Gallo of the NIH in the USA and research by virologist Berch Henry, Nevada. This research is cited in the book 'Oslers Web', by Hillary Johnson. Furthermore, HHV6a virus can infect the immune system cells and the nervous system and brain, all of which are affected in ME. These findings and other findings strongly suggest that HHV6a plays a key role in ME.

Chronic Lyme disease which has been found in many ME and CFS patients can aso cause B cell Lymphomas via long term TH2 cytokine dominance. This is a factor which is often overlooked in ME and CFS.

Recent research shows some similarities between Cancer and ME/CFS. Immunological abnormalities such as a dysregulated RNase L pathway, hyperactive NF-kappaB, increased oxidative stress and reduced NK cytotoxicity, among others, are present in both Cancer and ME/CFS, as found by Meeus et al. in 2009 (Immunological similarities between cancer and chronic fatigue syndrome: the common link to fatigue? Meeus et al. (2009) Anticancer Res. 2009 Nov;29(11):4717-26.). This intriguing finding corroborates other research findings from around the world confirming increased Cancer risk in ME/CFS patients.

Studies also show a thyroid cancer rate of 1 to 15 per 100,000 but in ME patients the rate is 6,000 per 100,000 (The International ME Conference, 2007, London. Dr. Byron Hyde). This is remarkable and represents a very significant risk of thyroid cancer in ME . This risk may relate to the thyroid and HPA axis dysfunctions consistently found in ME , and the Herpes virus infections (which can cause certain cancers) and continuing immune system dysfunction and autoimmunity, and oxidative damage to mitochondria, DNA, cells and tissues over time.

Furthermore, Dr. Heng of Wayne State University (USA) found serious chromosone breakage in 100% of ME/CFS patients using spectral karyotyping. 53% were identified as having chromosome translocations, often considered to be a recognized stepping stone of the cancer initiation process. Details provided on the NCF web site at http://www.ncf-net.org/PressReleases.htm#nfc. Following from this, there is a need to test for internal radionuclides and radioactive particles in patients. These would be sources of regular exposure to radiation, capable of causing serious chromosone damage. Some good research articles concerning radiactive particles in the environment and food chain and the development of Cancers, immune system, endocrine and neurological illnesses can be found at http://www.ncf-net.org/radiation.htm . The following paper analyses immune system abnormalities in ME and Cancer - Meeus M, Mistiaen W, Lambrecht L, Nijs J (2009), "Immunological similarities between cancer and chronic fatigue syndrome: the common link to fatigue?", Anticancer Res, Nov;29(11):4717-26, PMID: 20032425,

Dr. Uckun et al , recently published a paper  'Clinical Activity of Folinic Acid in Patients with Chronic Fatigue Syndrome'   In this article, the researchers found that 94% of the ME patients had a B-cell immunodeficiency with a marked depletion of their CD19+IgM+ mature B-lymphocyte population.  The CD19+IgM+ cells ranged from a low of 0.5% to a high of 53%.  These researchers concluded that there was "a high incidence of severe B-cell immunodeficiency" in ME patients. This correlates to clinical and scientific findings in the book Osler's Web mentioned above.

Following the same subject of B-cell abnormalities, there are many similarities between ME and Idiopathic CD4+ T lymphocytopenia. They are so similar that some people believe they are the same illness or that it is a subgroup of ME. Idiopathic CD4+ T lymphocytopenia has also been called non-HIV AIDS, which means it is an immune system deficiency and dysfunction without the HIV virus. B-cell abnormalities occur in Idiopathic CD4+ T lymphocytopenia, in a similar manner to the way they occur in ME. These B-cell abnormalities may be the initiating factors for autoimmunity and certain Cancers.

Virus infections tend to have multiple effects on the human body. There is a strong belief that a virus and / or mycoplasma causes the abnormality in the 2-5a synthetase / RnaseL anti-viral pathway & PKR pathway OR a virus and / or mycoplasma infects the Mitochondria and interrupts krebs cycle function and this domino effects on the immune system. New scientific findings in the USA show that a significant percentage of ME patients are or were infected by Parainfluenza Virus-5 (PIV-5). This particular virus targets and degrades the STAT1 protein in the immune system, and this in turn leads to immune dysfunction. The destruction of STAT1 protein is one of the main features of ME, in addition to RnaseL abnormalities, PKR abnormalities, p53 protein abnormalities and Actin abnormalities. There is continuing scientific research to establish if this virus is causative, opportunistic or a co-factor in the illness.

These scientific findings are supported by other research findings showing a number of autoimmune disorders resulting from Mitochondria damage / destruction in ME which have direct effects on immune system functions and other bodily functions - these are outlined in the paper 'Acute Phase Phospholipids Related to the Cardiolipin of Mitochondria in the Sera of Patients With Chronic Fatigue Syndrome (ME ), Chronic Ciguatera Fish Poisoning (CCFP), and Other Diseases Attributed to Chemicals, Gulf War, and Marine Toxins' Yoshitsugi Hokama et al. Journal of Clinical Laboratory Analysis 22:99–105 (2008). Autoimmunity is further corroborated by other research which shows the IgM isotype of ACA was present in 95% of ME patients tested. This is an unusually high percentage and is an important finding. It suggests autoimmunity as anticardiolipin antibodies have consistently been found in autoimmune diseases and some infectious diseases. This correlates to autoimmune and B-cell abnormalities found in ME and to the effectiveness of the autoimmune drug Rituximab in clinical investigations. Rituximab, a chimeric monoclonal CD20 antibody, has been shown to normalize high ACA serum titers of patients with autoimmune systemic lupus erythematosus, rheumatoid arthritis, autoimmune thrombocytopenia, and autoimmune hemolytic anemia. New research by Knox et al. suggests that the viruses consistently found in ME share molecular homologies for autoimmune disease markers of the thyroid, lupus, MS. These viruses may be invovled in molecular mimicry of some autoimmune markers (Knox, K., et al. Systemic Leukotropic Herpesvirus Infections and Autoantibodies in Patients with Myalgic Encephalomyelitis – Chronic Fatigue Syndrome. 7th International Conference on HHV-6 and 7. March 1, 2011. Reston, VA.). This may be the cause of the autoimmune disorders found in ME, and it may also explain the effectiveness of Rituximab an autoimmune drug. This is fascinating as ME patients have many of the neurological symptoms found in autoimmune illnesses of the thyroid, Lupus and MS and other autoimmune conditions.

The microbiome is important in ME and researchers have found significant gut dysbiosis in ME patients. This has important implications fo the immune system and autoimmunity as over 60% of immune cells are in the GI tract. Autoimmune research shows that the genes of microbes have been found to interact with human genes and it is believed that this may play a role in chronic disease ; this is the subject of ongoing research. The role of genes from the microbial metagenome, and the sum total of their interactions with human genes, cells and tissues over time in ME patients need to be fully investigated. In this context, infection, inflammatory immune damage, oxidative stress, and molecular mimicry need to be carefully investigated.

There is also scientific evidence of Antilamin antibodies in many ME patients, which suggests autoimmunity. Recent scientific research at Yale University shows that Epstein Barr virus (which has been found in many ME patients) can cause autoimmune reactions in patients, and re-activate latent endogneous viruses. B-cell abnormalities are involved in this autoimmunity and this leads the author to suggest that the drug Rituximab may have a beneficial role in combatting viruses and autoimmunity. He also recommends anti-viral therapy for some autoimmune conditons. (Autoimmune disease: A role for new anti-viral therapies? Dreyfus DH. Autoimmun Rev. 2011 Dec;11(2):88-97.). This is important considering the role of B cell abnormalities, autoimmunity and the drug Rituximab in ME.

Research is showing that deep tissue infections and bone and cartilage infections and nerve system infections are playing a role in some autoimmune illnesses. These infections are difficult to diagnose and find and many patients have been neglected. The immune system is attacking its own tissues, cells, cartilage, bone, nerves, etc. trying to get at viruses, bacteria, mycoplasma, pathogens, with resultant inflammation and serious damage over time. Chronic infections would lead to cell depletion, tissue depletion, cartilage, connective tissue and bone depletion, nerve tissue depletion, etc. at the point of chronic immune activation and inflammation. And the immune system is creating antibodies to human cells, tissue, glands, etc. in the process, thus giving the impression of autoimmunity. Consultants should be taking biopsies of acute AND chronically inflamed tissues, cartilage, and bone and testing them for various infections ?

All of this begs the following questions:
- are certain viruses and pathogens infecting B cells and using the machinery of these cells to create autoimmune conditions, continuing infection and immune dysfunction OR
- are pathogens infecting tissues, joints, bones, ligaments and causing immune system cells to react against these human tissues OR
- are pathogens which integrate and contain human tissue / cell markers causing an autoimmune reaction OR
- are pathogens mimicking human tissue / cell markers OR
- is human cell debris from oxidative stress and damage causing an autoimmune response OR
- do pathogens contain proteins or molecules which block immune response OR
- do pathogens contain similar proteins to that in surrounding human tissue OR
- are polymorphisms, mutations, predispositions, epigenetics, and changes in human genes from environmental factors and toxins causing autoimmunity

Autoimmune factors found in ME / CFS patients may be arising from one or more of these dynamics, this area is the subject of ongoing research.

Wider Autoimmune Aspects
The autoimmunity factors in ME and CFS are analysed in some detail in the following research papers.
The emerging role of autoimmunity in myalgic encephalomyelitis/chronic fatigue syndrome (ME/cfs). Morris G, Berk M, Galecki P, Maes M.. Mol Neurobiol. 2014 Apr;49(2):741-56.

Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Parallels with Autoimmune Disorders. Ekua W. Brenu Lotti Tajouri, Kevin J. Ashton, Donald R. Staines and Sonya M. Marshall-Gradisnik. 2013.

In MS, B cells with these markers CD19+ CD27+ CD38- CD138- CD19+ CD38+ CD138+ in the spinal fluid and blood stimulate cytokines and immune activation and accompanying damage to the nervous system. The dysregulation of B cells enables the survival of certain viruses such as EBV which has been linked to the central nervous system (CNS) infection in MS (Opsahl and Kennedy, 2007). In such cases the presence of EBV infected B cells promotes the persistence of EBV in the brain (Buljevac et al., 2005) and accompanying neurological degneration in MS. And in ME, B cells have also been found to be dysregulated and EBV (active and latent) plays a role in some subgroups.

New research in 2012 into MS and autoimmunity factors has implications for ME, and many other autoimmune and neurological illnesses. The research suggests that latent viral infections hiding within the immune cells or other body cells, can produce chemicals (containing some RNA) which can cause the immune system to become highly activated, causing inflammation and accompanying damage to human cells, tissues, nerves, myelin sheaths, etc.. This gives the impression of an autoimmune response as it appears to be human cells and tissue being attacked by the immune system. The latent virus is not picked up in many diagnostic tests as it is not fully active, and latent viruses are rarely treated, thus a condition is allowed to become chronic and degenerative over time.

Association of innate immune activation with latent Epstein-Barr virus in active MS lesions.
Tzartos JS, Khan G, Vossenkamper A, Cruz-Sadaba M, Lonardi S, Sefia E, Meager A, Elia A, Middeldorp JM, Clemens M, Farrell PJ, Giovannoni G, Meier UC. Neurology. 2012 Jan 3;78(1):15-23.

Link between MS and latent viruses and inflammation (2012).Queen Mary University of London.

Could the Epstein-Barr Virus – Autoimmunity Hypothesis Help Explain Chronic Fatigue Syndrome ? Simmaron Research 2014

There is a famous case of a British woman who was diagnosed with MS in a hospital and received treatments for MS. After some time, she decided to do a chronic Lyme disease test. She tested positive for Lyme disease and received treatments for this and recovered. She did not have MS, but the results of brain scans and neurological tests for MS were identical to those for chronic Lyme disease. This a remarkable new medical finding, and shows that infections of the brain and nervous system can appear like the symptoms of MS - http://www.dailymail.co.uk/health/article-2343062/Mother-diagnosed-MS-facing-life-wheelchair-cured--discovered-symptoms-TICK-BITE.html. ME shares many characteristics with MS and chronic Lyme disease and many forms of encephalitis and Meningitis and they are classified as neurological illnesses. Yet there is a reluctance by doctors, specialists and researchers to decipher the reasons for the lesions in the brain and nervous system in ME, and the underlying infectious agents (both active and latent) which play a role in neurological illnesses.

Viral and other pathogen infections both active and latent play a key role in ME. In some instances, latent viruses have become reactivated through immune system weaknesses, methylation failure and other viral infections. And new intriguing research shows that HHV6a virus has become chromosonally integrated into the genes of some patients. These outcomes are affecting T-cells and B-cells in ways which have yet to be fully deciphered by scientists.

The work of Dr. Garth Nicolson suggests that mycoplasmas and viruses may be able to integrate host cell material into their own structures, thus initiating autoimmune responses by the immune system. This would lead to the immune system attacking areas of the body recently infected by these mycoplasmas and viruses.

The following research paper outlines biological similarities between Multiple Sclerosis and ME/CFS. There are intriguing similarities.

Myalgic encephalomyelitis/chronic fatigue syndrome and encephalomyelitis disseminata/multiple sclerosis show remarkable levels of similarity in phenomenology and neuroimmune characteristics. Gerwyn Morris, Michael Maes. BMC Medicine 2013, 11:205 doi:10.1186/1741-7015-11-205

The following diagram by Knox et al. (2011) shows some of the autoimmunity factors found in ME.

Source: Knox, K., et al. Systemic Leukotropic Herpesvirus Infections and Autoantibodies in Patients with Myalgic Encephalomyelitis – Chronic Fatigue Syndrome. 7th International Conference on HHV-6 and 7. March 1, 2011. Reston, VA..

Subgroups - Matrixes of Viral, Mycoplasma and Pathogen infections, Immune system dysfunctions and autoimmunity factors, Mitochondria and Krebs cycle dysfunctions, Endocrine and HPA axis dysfunctions, Methylation Cycle blocks, Nervous system and Autonomic system dysfunctions & other biological abnormalities

The scientific findings in the Scientific Evidence section of this web site provide a lot of scientific evidence of viral and bacteria infections in ME patients. And the recent medical findings of Dr. Martin Lerner (USA), Dr. John Chia, Dr. Kenny De Meirleir (Belgium) and findings in Australia (Peripheral blood gene expression in postinfective fatigue syndrome following from three different triggering infections. Galbraith S, Cameron B, Li H, Lau D, Vollmer-Conna U, Lloyd AR.. J Infect Dis. 2011 Nov 15;204(10):1632-40.) strongly support the fact that there are viral infections in patients and in some cases these co-exist with chronic Lyme disease, mycoplasma, babesia, chlamydia and parasite infections. It strongly suggests that a number of viruses are capable of causing ME and they can also act as a co-factor and /or opportunistic infection in the illness over time. And these infections are accompanied by immune system dysfunctions and autoimmunity which persists over a long period of time. The findings of Knox et al. (2011) show the importance of Herpes infections in ME.



Source: Knox, K., et al. Systemic Leukotropic Herpesvirus Infections and Autoantibodies in Patients with Myalgic Encephalomyelitis – Chronic Fatigue Syndrome. 7th International Conference on HHV-6 and 7. March 1, 2011. Reston, VA..

The scientific and medical findings of Dr. John Chia in California confirm that viral and bacteria infections play a role in ME, and in subsets of ME patients. Dr. Chia's scientific findings are listed below.

Source: Clinical Infectious Diseases. 2003; 36:671–2. Chia.

The following videos are brief lectures by top medical doctors on the role of infections and immune system abnormalities. And the medical diagnosis and treatments used in some of the more successful ME clinics. They provide an excellent introduction to the illness and its treatment.

 

 

Dr. John Chia, is medical doctor based in California, who is world renowned for his work, particuarly with Enteroviruses. He has been treating ME / CFS pateints and researching the illness since the late 1990's. He has found that Enteroviruses are present in some subgroups of ME patients and that treating these Enterovirus infections can lead to significant improvement and recovery.

Enteroviruses have been associated with ME since the 1930's. Names such as 'Epidemic  Neuromyasthenia’,  ‘Encephalitis’,  ‘Akureyri Disease’, ‘atypical poliomyelitis’, 'Iceland disease',  ‘poliomyelitis-like epidemic neuromyasthenia’, 'diencephalitis',  ‘Abortive Poliomyelitis’ were used to describe the illness prior to the term ‘Myalgic Encephalomyelitis’ being created by Dr. Melvin Ramsey in 1956. Enteroviruses were implicated in most epidemics from the 1930's to the present day.

" Primary M.E. is always an acute onset illness. Doctors A. Gilliam, A. Melvin Ramsay and Elizabeth Dowsett (who assisted in much of his later work,) John Richardson of Newcastle-upon-Tyne, W.H. Lyle, Elizabeth Bell of Ruckhill Hospital, James Mowbray of St Mary's, and Peter Behan all believed that the majority of primary M.E. patients fell ill following exposure to an enterovirus. (Poliovirus, ECHO, Coxsackie and the numbered viruses are the significant viruses in this group, but there are other enteroviruses that exist that have been discovered in the past few decades that do not appear in any textbook that I have perused.) I share this belief that enteroviruses are a major cause. "

Source: http://www.nightingale.ca/documents/Nightingale_ME_Definition_en.pdf

Dr. John Richardson, was a brilliant British doctor who spent over 30 years diagnosing and treating ME patients in Britain. He advised and mentored Dr. Byron Hyde. Dr. Melvin Ramsey is world famous for his contributions to ME research. Dr. Byron Hyde also has a good international reputation. ECHO 7 appears to be infecting significant numbers of ill people, including those with ME, ALS, Alzheimers, and Gulf War Illness.

His research paper provides some important insights - Chronic fatigue syndrome is associated with chronic enterovirus infection of the stomach. Chia JK, Chia AY. J Clin Pathol. 2008 Jan;61(1):43-8. Epub 2007 Sep 1. See diagram below:

Dr. John Chia presents his research findings up to the year 2011 to the National Institutes of Health (NIH) in the USA below:

Dr. Chia's work and findings are similar to those of John Richardson, a medical doctor who was based in Newcastle in England who treated ME patients from many parts of Britain for over 40 years. He developed an expertise in diagnosing the illness, and became one of the world's foremost experts in ME. He even used autopsy results from dead patients to investigate the illness. He found that Enteroviruses and toxins played a major role in ME, and that this led to immune dysfunction, neurological abnormalities, endocrine dysfunction, and over time to increased risk of cardiac failure, cancers, carcinomas, and other organ failure. He wrote a book about his medical experiences called Enteroviral and Toxin Mediated Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

The outbreak in Iceland was important, and provided some vital clues about the illness and the role of Enteroviruses.
"However, children in epidemic Neuromyasthenia areas responded to poliomyelitis vaccination with higher antibody titres than in other areas not affected by the poliomyelitis epidemic, as if these children had already been exposed to an agent immunologically similar to poliomyelitis virus (Sigurdsson, Gudnad6ttir Petursson, 1958). Thus, the agent responsible for epidemic Neuromyasthenia would appear to be able to inhibit the pathological effects of poliomyelitis infection. When an American airman was affected in the 1955 epidemic and returned home, a similar secondary epidemic occurred in Pittsfield, Massachusetts, U.S.A. (Hart, 1969: Henderson and Shelokov, 1959)."
Many outbreaks of ME or epidemic Neuromyasthenia worldwide followed an outbreak of polio virus.
Parish JG (1978), Early outbreaks of 'epidemic neuromyasthenia', Postgraduate Medical Journal, Nov;54(637):711-7, PMID: 370810.

Dr. Chia also presents his medical experiences in the videos below:

 

 



 

 

 

Dr. Martin Lerner is a medical doctor with 40 years experience. Certified by the American Board of Internal Medicine and is an Infectious Disease Specialist. Residency, Internal Medicine, Harvard Medical Services. Boston City Hospital and Barnes Hospital, St. Louis, MO. Washington University School of Medicine, M.D. Two Years, National Institute of Allergy and Infectious Diseases, Epidemiology Unit. 
Alumni Awardee, Washington University School of Medicine.

Three years research fellow in infectious diseases at the Thorndike Memorial Laboratory, Boston City Hospital and Harvard Medical School under the direction of *Dr. Maxwell Finland, (founder of subspecialty infectious diseases). Chief of the Division of Infectious Diseases and Professor of Internal Medicine at Wayne State University School of Medicine, 1963-1982. Established a clinical virology laboratory and trained 33 physicians in the subspecialty of infectious diseases, Wayne State University, 1963-1982.

The Treatment Center for Chronic Fatigue Syndrome which has successfully treated thousands of ME patients.

- Slides of Dr. Martin Lerner's lecture

Dr. Lerner has developed some useful diagnostic criteria for doctors based on his 20 years experience of the ilness.
ME/CFS Treatment Resource Guide for Practitioners by Dr. Martin Lerner

 

  Dr. Kenny De Meirleir is medical doctor based in Belgium and in Nevada in the USA. He runs a well known medical clinic in Belgium and also works for the Whittemore Peterson Institute in Nevada in the USA. He has been treating ME / CFS patients and researching the illness since 1990. He has seen thousands of ME / CFS patients over the years. The medical and scientific findings of Dr. Kenny De Meirleir over 20 years support the role of infections and immune system abnormalities in ME / CFS. Lecture series by Dr. Kenny De Meirleir videos 1 - 20, created in 2012 and 2013. Specifically for medical doctors and hospital consultants.
  • Commentary & Discussion
    Infections and immune system abnormalities in ME / CFS


 

  Dr. Edward J. Conley, D.O. Professor of Family Medicine at Michigan State University. His medical practise and clinic Fatigue, Fibromyalgia and Autoimmune Clinic, Michigan, USA has successfuly treated a few thousand CFS patients since 1994. He wrote this book 'America Exhausted ; Breakthrough treatments of fatigue and fibromyalgia' .The short video below gives an outline of the medical and scientific findings.


 

  Dr. Lucinda Bateman. Dr. Bateman is a highly respected and well experienced medical doctor who has been treating ME / CFS patients since the late 1990's. She is a medical graduate of the prestigious Johns Hopkins University in Maryland. Dr. Bateman runs an ME/CFS clinic in Utah in the USA which is visited by patients from many states throughout the USA. Her expertise in ME / CFS has been ackowledged by the US Government authorities and national patient organistions in the USA, who have asked her to serve on their committees and expert bodies.

 

Doctor training and patient information series - video lectures
For medical doctors and patients: Videos 1 - 30

More Video lectures by Dr. Lucinda Bateman & others


 

  Dr. Garth Nicolson is a professional scientific researcher based in Florida, USA. He has been researching pathogen infections and immune dysfunctions since the late 1980's. He runs the Institute for Molecular Medicine, and has carried out extensive research on hundreds of ME / CFS patients over the years. The scientific and medical findings of Dr. Garth Nicolson (USA) has consistently found that high percentages of ME patients have mycoplasma infections. A significant percentage also have co-infections including HHV6a and various bacteria infections. This correlates to illness severity. Dr. Nicolson also found evidence of immune dysfunctions. This ties into the work of other scientists and doctors who have consistently found viral, mycoplasma and other pathogen infections, along with immune dysfunction in ME patients.




 

  Dr. Ritchie Shoemaker is a medical doctor based in Maryland, USA. He is one of the top experts on mycotoxins in the world. He has been treating ME / CFS patients since the late 1990's, and he believes that myctoxins are a major factor in some ME / CFS subgroups and in other illnesses. Mycotoxins are accepted by the CDC and NIH in the USA as being hazardous to health. Lecture below on the effects of chronic mycotoxins and mold exposure on the immune system, endocrine system and nervous system.
Dr. Paul Cheney, Dr. Meirleir and Dr. Peterson (mentioned above) are now using tests for mycotoxins as part of their diagnostics protocol for ME / CFS.

 





These medical doctors are clear that one must identify the infections present and identify the subsets of patients and then treat these infections so as to bring about recoveries from ME. It is well known that Cognitive Behaviour Therapy (CBT) and Graded Exercise Therapy (GET) cannot treat these infections in ME and thus cannot treat ME. This is a scientific and medical fact.

Further corroborating scientific evidence of viral infections and bacteria infections in ME is provided by Harvard Medical School Professor Anthony Komaroff and Neurologist Tracey Cho in their recent paper ' Role of Infection and Neurologic Dysfunction in Chronic Fatigue Syndrome.' Anthony L. Komaroff, Tracey A. Cho. Semin Neurol 2011; 31(3): 325-337. In this paper they reviewed scientific, medical and clinical findings over many years, and found evidence of infection by pathogens and immune dysfunction and neurological dysregulation in ME / CFS. These scientific findings are backed up by ground-breaking research in 2010 and 2011 by Dr. Martin Lerner, a highly esteemed medical doctor and researcher in the USA who has been treating / researching ME since the mid 1990's. Dr. Martin Lerner has found that some of these viruses have special characteristics:

- abortive lytic replication (EBV, CMV, HHV-6a) producing host cell apoptosis as described by Dr. Martin Lerner.
- IgM antibody to non-structural gene products (resulting from abortive lytic replication) as described by Dr. Martin Lerner
- coexisting infection by bacteria, mycoplasma, babesia, chalmydia, Lymes disease.
- this type of infection causes an increase in a protein called dUTPase, a biomarker
Treating and eliminating these infections (over many months) has resulted in recoveries from ME. The above markers are a very important scientific discovery and could be one of the main bio-markers for ME.

In severely ill ME patients, Dr. Kenny De Meirleir has found intestinal overgrowth of Gram positive D/L lactate-producing bacteria which are known to produce H2S (hydrogen sulfide) in the presence of certain heavy metals as a survival defense mechanism. The toxin H2S produces a lot of oxidative stress and damages mitochondria, the intestines, the immune system, nervous system and muscle tissue. It is a major factor in some subgroups of ME and may be the causative factor.

A parasite Cryptostrongylus pulmoni has been found in over 60% of ME patients in research and clinical practise. This particular parasite attacks the immune system, and causes immune dysregulation. It also secretes peptides which can adversely affect brain function, the nervous system, blood flow, the hypothalmus and the HPA axis in humans. All of these play a key role in ME. This infection may be causative or a co-factor or an opportunistic infection arising from immune system weaknesses.

Subgroups
The scientific findings support the existence of subgroups in ME, and these subgroups correlate to different matrixes of viral and pathogen infections, immune system dysfunctions, autoimmunity, HPA axis abnormalities, neurological dysfunctions, toxin loads, mitochondria and krebs cycle abnormalities, methylation cycle blocks, etc. This has been confirmed by some recent genetic research :

- Differentially expressed genes in Chronic Fatigue Syndrome / Myalgic Encephalomyelitis (ME /ME) patients reveal seven subtypes with distinct clinical phenotypes. Kerr JR, Petty R, Burke B, Gough J, Fear D, Sinclair LI, Mattey DL, Richards SC, Montgomery J, Baldwin DA, Kellam P, Harrison TJ, Griffin GE, Main J, Enlander D, Nutt DJ, Holgate ST. Journal of Infectious Diseases 2008;197:1171-84.

- Seven genomic subtypes of Chronic Fatigue Syndrome / Myalgic Encephalomyelitis (ME /ME): a detailed analysis of gene networks and clinical phenotypes. Kerr JR, Burke B, Petty R, Gough J, Fear D, Mattey DL, Axford JS, Dalgleish AG, Nutt DJ. Journal of Clinical Pathology 2008;61:730-9

- Microbial infections in eight genomic subtypes of chronic fatigue syndrome/myalgic encephalomyelitis. Zhang L, Gough J, Christmas D, Mattey DL, Richards SC, Main J, Enlander D, Honeybourne D, Ayres JG, Nutt DJ, Kerr JR.. J Clin Pathol. 2010 Feb;63(2):156-64.

Lessons from Cancer
Many illnesses such as Cancer have subgroups, which means there are slight variations in the illness between sets of patients. This may be due to inherited genetic factors, environmental exposures, interactions of genes with the environment and mutations, polymorphisms and gene expression changes, differing immune systems and reactions, different pathogen exposures, and triggering mechanisms for the illness.

The eminent Dr. Stephen Holgate in Britain, stated recently there are 15 subgroups in breast Cancer and he believes that there are many subgroups in ME and CFS. There would be general agreement with him on this by most ME and CFS doctors and scientists and patients. There are some heterogeneous features in a distinct illness such as ME and CFS.  As diagnostic methods and technologies improve over time, including genetic technologies, there will be (i) greater precision attained in the diagnosis of illnesses (ii) some illnesses will have their subgroups identified, classified and defined with greater precision (iii) illnesses which were once thought to be just one illness will be found to be a number of undiagnosed illnesses, and they will be split into separate illnesses as a result ; each having their own distinct bio-markers, genetic markers and symptoms. This will bring greater clarity into medical and scientific understandings of chronic physical illnesses such as ME.

For ME and other physical illnesses, these subgroups may be due to :

- inherited genetic factors, including genetic weaknesses and susceptibilities

- environmental exposures, including toxins and levels of oxidative stress in the body. And the interactions of genes with the environment, including toxins, pagthogen genes, and oxidative stress factors. The changes to the genes and to gene expressions.

- different triggering mechanisms for the illness

- the initial strength and status of one's immune system and it's susceptibility to viral / toxin induced immune dysfunction

- different pathogen exposures over time. This would include chronic sub-clinical focal infections and other infections.

- excessive chronic stress over a prolonged period of time, with a near constant 'fight or flight' response, causing shut down or slowing down of some body functions in order to survive, which disrupts glucose, oxygen and nutrient uptake at cellular level, and this in turn has negative and destructive effects on mitochondria function and the krebs cycle, immune system function, and HPA axis function. Adrenal exhaustion playing a significant role.. Many scientific studies have found that excessive stress lies at the root of many Cancers, heart attacks, strokes, diabetes, and other physical illnesses.

- geographical location

- the matrix of infections present in the patient. Including viruses, mycoplasmas, bacteria, candida, parasites.

- the matrix of Mitochondria and Krebs cycle dysfunctions, Immune system dysfunctions and autoimmunity factors, Endocrine and HPA axis dysfunctions, Methylation Cycle blocks, Central nervous system and Autonomic nervous system dysfunctions & other biological abnormalities present in the patient

- the progression of the illness over time. The accumulated damage and domino effects. And what stage of the illness a patient is in. Is it stage 1, 2 or 3.

For example ME has subgroups with the following characteristics

Subgroup 1 - virus a, virus d, mycoplasmas, mitochondria and krebs cycle abnormalities, central nervous system damage and brain damage, genetic factors a, r, l, n, methylation cycle blocks, immune system dysfunctions a, c and f, autoimmunity factors a, HPA axis dysfunctions, low circulating blood volume, sleep abnormalities, moderate heavy metal burden in body, Orthostatic intolerance and POTS, gastro-intestinal problems, brain lesions, serious mobility impairment, chronic allergies and/or sinusitis, stage 3 of the illness, serious cognitive impairment
Subgroup 2 - virus e, parasites, chronic Lyme disease, mitochondria and krebs cycle abnormalities, central nervous system damage and brain damage, genetic factors r, f, q, b, methylation cycle blocks, immune system dysfunctions a, b, c and e, autoimmunity factors a,b, HPA axis dysfunctions, low circulating blood volume, sleep abnormalities, high heavy metal burden in body, skin rashes, gastro-intestinal problems, chronic pain, stage 1 of the illness, chronic allergies and/or sinusitis, higher Cancer risk
Subgroup 3 - virus a, mycoplasmas, chlamydia, mitochondria and krebs cycle abnormalities, genetic factors l, n, d, h, methylation cycle blocks, central nervous system damage and brain damage, immune system dysfunctions a, b and d, autoimmunity factors a, b,d, HPA axis dysfunctions, low circulating blood volume, sleep abnormalities, moderate heavy metal burden in body, brain lesions, serious cognitive impairment, chronic allergies and/or sinusitis, Orthostatic intolerance and POTS, stage 2 of the illness, serious mobility impairment, cardiac abnormalities and higher heart attack risk
Subgroup 4 - virus d, mycoplasmas, babesia, toxins b,e, mitochondria and krebs cycle abnormalities, genetic factors, b, l, f, e, methylation cycle blocks, central nervous system damage and brain damage, immune system dysfunctions a and f, HPA axis dysfunctions, sleep abnormalities, autoimmunity factors a, b, c, intestinal dysbiosis, moderate heavy metal burden in body, low circulating blood volume, gastro-intestinal problems, chronic allergies and/or sinusitis, chronic pain, stage 2 of the illness, Orthostatic intolerance and POTS, cardiac abnormalities and higher heart attack risk
Subgroup 5 - mycoplasmas, chronic Lyme disease, mitochondria and krebs cycle abnormalities, toxins a,c,e, genetic factors s, h, g, e, central nervous system damage and brain damage, methylation cycle blocks, immune system dysfunctions a, b, d and e, HPA axis dysfunctions, gastro-intestinal problems, low circulating blood volume, high heavy metal burden in body, sleep abnormalities, skin rashes, chronic allergies and/or sinusitis, autoimmunity factors a,d, brain lesions, stage 3 of the illness, serious cognitive impairment, higher Cancer risk

Factors in common: immune system dysfunction a, mitochondria and krebs cycle abnormalities, methylation cycle blocks, HPA axis dysfunctions, low circulating blood volume, sleep abnormalities, autoimmunity factor a, heavy metal burden in body, central nervous system damage and brain damage, chronic allergies and/or sinusitis,. Subgroups differ slightly in infections, toxin exposures and loads, immune system dysfunctions, Orthostatic Intolerance and POTS, chronic pain and the degree of pain, brain lesions, gastro-intestinal problems, onset of the illness and age at onset, the duration of the illness and the degree of accumulated damage, the stage of the illness, and in heart attack risk and Cancer risk.

Genetics: some similarities between subgroups but some differences between subgroups. This may appear contradictory but it is not. Genetic expressions reflecting slightly different disease processes and biological dysfunctions and abnormalities in patients. This arising from different triggering mechanisms for the illness, different genetic inheritances and genetic weaknesses and susceptibilities, environmental exposures and genetic mutations and polymorphisms, oxidative stress factors, the initial strength and status of one's immune system and it's susceptibility to viral / toxin induced immune dysfunction, geographical location, different pathogen exposures, and the progression of the illness over time.

Treatment Implications: This will involve several diagnostic tests to identify all infections and immune system dysfunctions and autoimmunity factors, mitochondria and krebs cycle abnormalities, methylation cycle blocks, HPA axis abnormalities, and other biological abnormalities and dysfunctions in an ME patient. And then treating the main or primary abnormalities and dysfunctions and infections first. And after this, moving on to treat other biological abnormalities and dysfunctions. Dr. De Meirleir (Belgium) has had great success with Ampligen combined with anti-viral and anti-pathogen treatments in his clinic in Belgium. Firstly, all of the infections were identified through several intensive diagnostic tests. Then Ampligen was combined with specific anti-viral and anti-pathogen treatments. Treatment is given for several months and up to a year. The results were impressive, and patients recovered from ME. Dr. De Meirlier has stated that an eight-year follow-up of patients found that 92% had not relapsed. This is highly significant. This strongly indicates that Ampligen by itself may not be enough, but combining it with anti-viral and anti-pathogen treatments may bring about better improvement and a high probability of full recovey. This was reported in the AAME Conference of 2001, click here to view paper. This mode of treating several infections and dysfunctions at once is supported by Dr. Martin Lerner, Dr. Edward J. Conley and other ME specialist doctors.

The reactivation of latent and endogeneous viruses may be caused by pathogen infection / toxin exposure which adversely affects immune system function, and weakens it significantly and/or failures in methylation and/or mitochondria and the krebs cycle.


Scientific Research Priorities


(i) Developing and Building upon Past Research Findings & Biomarkers

(a) New research will need to make more use of Biobanks which contain several samples from thousands of ME and CFS patients . The following scientific markers and tools will need to be used and some research findings and areas replicated (see below):

  • use of electronic scans, imaging scans and signatures, spectral and spectroscopic scans and signatures, EMF scans and signatures and genetic signatures technologies to efficiently and accurately scan blood samples, spinal fluid samples, nerve tissues, brain sites, spinal sites, nervous system sites, intestinal tissues, thyroid gland sites, liver sites, adrenal gland sites, blood vessel tissues, and immune cells for infections and infectious signatures of known, and new and emerging viruses, bacteria, parasites and mycoplasmas
  • new technologies for rapidly identifying abnormalities in immune system cells and subsets, immune cell molecular markers, cytokines and cytokine networks and inflammatory markers such as C Reactive protein, TNF, NFκB and COX2. Integration of real time biological tracking technologies with smart technologies to assess progress or regress in patients.
  • technology to rapidly identify genetic markers, gene expression markers, genetic mutations and polymorphisms and their role in the illness
  • technology to rapidly identify abnormal molecular markers, miRNA's in the illness
  • proteomic markers, spinal fluid and other neurological markers
  • Metagenome. Deeper testing and analysis of viruses, mycoplasma and Microbiota of bacteria which include L-form, biofilm, and intracellular bacterial forms
  • Microbiome factors influencing the immune system and nervous system, the illness development and perpetuation.
  • use of brain imaging technologies such as SPECT, PET, MRS, MRI, fMRI to detect brain abnormalities
  • use of Metabolomics to identify abnormalities in metabolism and cellular functions.
  • new imaging technologies and techniques to measure biological processes, functions and structures inside the human body. And differentiate healthy cells and tissues and activities from infected and inflamed cells and tissues and activities. Detect neuro-inflammation in the brain, spinal cord and nervous system.
  • testing of inflamed nerve tissues, muscle tissues and intestinal tissues
  • analysis of sub-cellular factors with wide ranging effects on the body - Mitochondria abnormalities and Methylation cycle blockages.
  • urinary and other metabolites
  • live blood analysis and analysis of multiple blood subsets, live infections, coagulation markers, and molecular markers.

    Listing of Research findings and papers worldwide
    which need to be replicated or deciphered in more depth
  1. Immune system dysfunction and abnormalities
  2. Genetic markers
  3. Severely Damaged Mitochondria and Defective Krebs cycle and ATP production
  4. Viral infections
  5. Mycoplasma infections
  6. Serious Bacteria infections
  7. Molds & Mycotoxins & Immune Dysfunctions
  8. Cryptostrongylus Pulmoni infection
  9. Increased risk of Cancer
  10. Environmental Toxins, Heavy Metals, Organophosphates
  11. Orthostatic intolerance & Postural orthostatic tachycardia syndrome (POTS) & Body fluid abnormalities
  12. Serious Brain and nervous system abnormalities
  13. Spinal Fluids & Proteomic Markers
  14. Cognitive Dysfunctions & 'Brain Fog'
  15. Effects of Exercise, GET and CBT
  16. Muscle abnormalities
  17. Abnormal HPA axis (Hypothalmus Pituary Adrenal axis) & Abnormal glandular functions
  18. Intestinal Abnormalities and Microbiome
  19. Cardiac and Vascular and Blood vessel problems. Increased risk of heart attack
  20. Idiopathic CD4+ T lymphocytopenia
  21. Methylation cycle blocks and glutathione deficiency
  22. Increased oxidative stress
  23. Channelopathy & Disturbance in the way certain ions (mainly sodium and potassium salts) are transported in and out of cells across the cell membranes
  24. Sleep abnormalities
  25. Ciguatera and ME
  26. Telomere shortening
  27. Abnormal red blood cell structure
  28. Inability to metabolise glucose and sugar
  29. Defects in Lymphatic Drainage
  30. Lowered oxygen consumption in ME patients
  31. Substance P is elevated in ME patients
  32. Abnormal Plasma RNA's
  33. Abnormal Urinary metabolites
  34. The presence of crimson crescents in the mouth
  35. Beta 2 microglobulin levels as a measure of the severity of the condition
  36. Abnormal levels of serum Chromogranin-A. Evidence of Celiac disease in some ME patients
  37. Skin rashes, acne and allergies worsen after the onset of ME
  38. Clonal Excess Abnormality
  39. Other Serious Abnormalities
  40. Sub-groups within ME

ME/CFS and Medical Abnormalities - Medical Research paper. This paper details many of the biological abnormalities, dysfunctions and infection found in ME and CFS patients and research papers to support this.

The Dubbo Studies which were published in leading medical journals verify much of the above, and point to genetic factors, environmental factors and a post-infectious dysfunctional immune system as being the key factors in ME / CFS.

Post-infective and chronic fatigue syndromes precipitated by viral and non-viral pathogens: prospective cohort study. Hickie I, Davenport T, Wakefield D, Vollmer-Conna U, Cameron B, Vernon SD, Reeves WC, Lloyd A; Dubbo Infection Outcomes Study Group. BMJ. 2006 Sep 16;333(7568):575. Epub 2006 Sep 1.

Cytokine polymorphisms have a synergistic effect on severity of the acute sickness response to infection. Vollmer-Conna U, Piraino BF, Cameron B, Davenport T, Hickie I, Wakefield D, Lloyd AR; Dubbo Infection Outcomes Study Group. Clin Infect Dis. 2008 Dec 1;47(11):1418-25. doi: 10.1086/592967.


(ii)
Structure of Causation and Continuation


(a)
Can acute infections lead to chronic infections and illnesses, and reactivations of latent viruses and bacteria migrating to other body organs ? and other biological abnormalities ?

O'Connor et al. (2006) at the Centers for Disease Control and Prevention state, “At least 13 of 39 recently described infectious agents induce chronic syndromes.” Science is continuing to uncover the impact of acute virus, mycoplasma and bacteria infections in the development of chronic illness. See Emerging infectious determinants of chronic diseases. O'Connor SM, Taylor CE, Hughes JM. Emerg Infect Dis. 2006 Jul;12(7):1051-7.



Source: Emerging infectious determinants of chronic diseases. O'Connor SM, Taylor CE, Hughes JM. Emerg Infect Dis. 2006 Jul;12(7):1051-7

"For example, fully 10% of people who suffered from E. coli food poisoning later developed a relatively infrequent life-threatening complication called hemolytic uremic syndrome (HUS) where their kidneys and other organs fail. (3) Approximately two-thirds of patients with Guillain-Barre syndrome, a suspected autoimmune syndrome, have a history of an antecedent respiratory tract or gastrointestinal infection. (4) Campylobacter infection is the most commonly identified precipitant of GBS and can be demonstrated in as many as 30 percent of cases. (5) Reactive arthritis (Reiter's syndrome) is another excellent example. Reactive arthritis is classically seen following infection with enteric pathogens such as Yersinia, Salmonella, Campylobacter and Shigella. (6) In a 2006 study, Alan S. Brown of Columbia University showed that prenatal infections such as rubella, influenza, and toxoplasmosis are all associated with higher incidence of schizophrenia. (7) Brown found a seven-fold increased risk of schizophrenia when mothers were exposed to influenza in the first trimester of gestation. One final example: a 2010 study concluded that cesarean delivery is associated with 1.8 times higher risk of celiac disease but not inflammatory bowel disease in children. (8)"

"A case-controlled study of residents of the Isle of Man found that 40 percent of people with sarcoidosis had been in contact with a person known to have the disease, compared with 1 to 2 percent of the control subjects.(12) Another study reported three cases of sarcoidosis among ten firefighters who apprenticed together.(13) A cluster of 13 cases of Parkinson's disease among a community of 592 people were reported in Israel, significantly more that would be expected by chance.(14) Research suggests that obesity is also an inflammatory disease caused by certain species of the Th1 pathogens. A study recently published in the New England Journal of Medicine found that a person's risk of becoming obese increases by 57% if they have a friend who becomes obese, and by 37% if their spouse becomes obese.(15) According to the researchers: "These clusters did not appear to be solely attributable to the selective formation of social ties among obese persons." "
Source: http://mpkb.org/home/pathogenesis/evidence_bacteria

Jang et al. (2009) at St. Jude Children's Research Hospital, USA, discovered that an H5N1 Bird Flu (strain A/VN/1203/1204) infection in mice causes severe loss of tyrosine-hydroxylase positive dopaminergic neurons 60 days after infection by provoking a destructive autoimmune response, thus suggesting the infection by certain strains of flu might increase the risk of Parkinson's disease in humans.
Source: Haeman, Jang; David Boltz; Katharine Sturm-Ramirez; Kennie R. Shepherd; Yun Jiao; Robert Webster; Richard J. Smeyne (2009-08-10). "Highly pathogenic H5N1 influenza virus can enter the central nervous system and induce neuroinflammation and neurodegeneration". Proceedings of the National Academy of Sciences 106 (33): 14063–8.

The scientific research findings of Dr. Garth Nicolson show that co-infections are common in those people with chronic illness. We have provided listings of his research papers on this web site. In her speech at the International Congress of Autoimmunity, Amy Proal stated that of the Marshall Protocol subjects with Hashimoto's thyroiditis who participated in a survey, only 8% with Hashimoto's had Hashimoto's alone. The Hashimoto's patients had at least one, sometimes several comorbidities or co-infections. The same has been found in other patients with autoimmune and chronic illnesses, while they were receiving Marshal Protocol treatment.

Research by Morris et al. (The Putative Role of Viruses, Bacteria, and Chronic Fungal Biotoxin Exposure in the Genesis of Intractable Fatigue Accompanied by Cognitive and Physical Disability, 2015) points to the effects of past infections and continuing chronic infections in the perpetuation of ME over many years or decades. Parvoviruses, HHV6, variants of Epstein-Barr, Cytomegalovirus, Mycoplasma, and Borrelia burgdorferi and Mold infection are mentioned. This would create some differences and subsets between patients.

(iii) Immune Dysfunctions and Associated Infections
Replication studies to further develop a biological systems model needs to be undertaken to explain the abnormalities in Immune system subsets & associated genes

(a) B cell abnormalities, Infections and Autoimmunity
A biological systems model needs to be developed through scientific trials, experiments and studies to explain

  • why does Rituximab, an anti-Cancer drug and autoimmune drug, lead to full recoveries from ME ? what are the biological and molecular pathways involved ? and are there other safer drugs which can do this ? are B-cells incubating and carrying a virus (latent or active) or mycoplasma or bacteria or other pathogen in ME patients causing an infection, immune activation, immune dysfunction and autoimmunity ? are B cells cells carrying cellular / genetic material of these pathogens ? Dr. Martin Lerner believes that B cells may be carriers or transport mechanisms for pathogens.
  • the exact role of B-cells and the various B-cell abnormalities, including:
    • all B cell markers in ME
    • B cell autoantibodies in ME
    • B cell autoimmune markers and instigators in ME.
    • B cell markers coding for inflammation and autoimmunity
    • B cell memory and formation in ME
    • bone marrow B-cell lineage in ME
    • genetic changes to B cell numbers and functions in ME
  • map the direct effects of the following on B cells, including infection of B cells and B cell activations / responses:

    Viruses include: HHV6a virus, Herpes family viruses 1-8, Parvovirus B-19, CMV, Coxsackie viruses, Enteroviruses, Ross river virus, Q fever virus, Stealth virus, JHK virus,  Parainfluenza Virus-5 (PIV-5), Paramyxovirus and measles viruses of the  Paramyxoviridae family, Cryptovirus, Borna virus, HTLV family viruses, HGRV virus in spinal fluids, nerve tissues, blood, brain, intestines, and muscles. Retroviruses are important, as Retrovirus sequences were found in 85% of ME cases, and Anellovirus found in 75% of ME cases in research conducted by Dr. Hornig and Dr. Lipkin in Columbia University in September 2013. Most of these viruses listed here would include chronic, low level, sub-acute infections which inflict damage and immune activation, but which may not show up in standard or outdated tests.
    Reactivated latent viruses include HERV-K18, Varicella-Zoster virus, Herpes family viruses 1-8, measles viruses of the  Paramyxoviridae family. Some viral infections can reactivate latent viruses and undermine immune system functions.

    Mycoplasma: M. fermentans, M. penumoniae, M. hominis, M. penetrans, M. pirum,  M. incognito. in intestines, spinal fluids, blood, brain, nerve tissues, muscles. These mycoplasmas would include chronic, low level, sub-acute infections which inflict damage and immune activation, but which may not show up in standard or outdated tests.
    Bacteria: Chronic Lyme disease, Ehrlichia, Bartonella, Brucella, Rickettsia, Chlamydia pneumonia, Staphylococcus spp. (live blood analysis), and Bacteria, including Microbiota of bacteria which include L-form, biofilm, and intracellular bacterial forms in spinal fluids, intestines, blood, brain, nerve tissues, muscles. Intestinal overgrowth of Gram positive D/L lactate-producing bacteria which are known to produce H2S (hydrogen sulfide) in the presence of certain heavy metals as a survival defense mechanism (Dr. Kenny De Meirleir). These bacteria would include chronic, low level, sub-acute infections which inflict damage and immune activation, but which may not show up in standard or outdated tests.
    Parasite: Cryptostrongylus pulmoni, Babesia, Candida, Giardia lamblia, Aspergillus Niger
    Molds, Bacteria and Mycotoxins in water damaged buildings: Stachybotrys family of molds, Cladosporium, Penicillium, Alternaria, Aspergillus, mycobacteria, Actinomycetes, Lipopolysaccharides (LPS), Microbial Volatile Organic Compounds (VOCs), Hemolysins. These can cause chronic inflammatory immune response and immune dysfunction over time.
  • Why is there Elevated B-cells with CD20 marker ? what is causing it ?
  • Why are naïve B cells a high percentage of all B cells.  Why are there lowered levels of IL 21,12, and 27, which are involved in the maturation of B cells.?

  • why is the following found in ME patients ? what is causing it ? and can it be blocked, prevented, or reversed ?

' patients had greater numbers of naive B cells as a percentage of lymphocytes: 6·3 versus 3·9% in HC (P = 0·034), greater numbers of naive B cells as a percentage of B cells: 65 versus 47% in controls (P = 0·003), greater numbers of transitional B cells: 1·8 versus 0·8% in controls (P = 0·025) and reduced numbers of plasmablasts: 0·5 versus 0·9% in controls (P = 0·013). While the cause of these changes is unclear, we speculate whether they may suggest a subtle tendency to autoimmunity.'
(Bansal et al., (2013), Altered functional B cell subset populations in patients with chronic fatigue syndrome compared to healthy controls. Clinical & Experimental Immunology, 172: 73–80.)

  • are mature or immature B-cells or bone marrow B-cells implicated ?

  • is the "programming" or immunological memory of new or naieve B cells defective ? and if so, then why ?

  • what are the relationships between B Cell abnormalities in ME and increased risk of non Hodgkins Lymphoma and it's subtypes - diffuse large B cell lymphoma and marginal zone lymphoma ? In the book Osler's Web: Inside the Labyrinth of the Chronic Fatigue Syndrome Epidemic by Hillary Johnson medical doctors in the USA found an unusually high number of B cell lymphomas in ME patients. Special scientific tests showed that these B-cell Lymphomas in ME patients were unusual types, not seen before. The researchers found B-cell deficiency in all patients, and a positive result on the kappa/lambda assay for a majority of these patients. After studying samples from approximately fifty patients, Wormsley estimated that the rate of clonal excess abnormality in the CFS patients from Nevada was at least 25 percent ('Oslers Web, by Hillary Johnson, Penguin Books 1997, page 94). This is significant as kappa/lambda light chains are the result of abnormalities within the bone marrow B-cell lineage. This has direct on B-cells and overall immunity, and susceptibility to Cancers. Recent scientific studies show that the incidence rate of non-Hodgkin's lymphoma is 0.02% in the United States, yet nearly 5% of CFS patients develop the disease. This is a significant risk factor.

  • can the specific antibody markers and autoimmunity markers on B cells be identified in ME patients ? and what role do they play in the overall illness ?

  • what role do the B cell receptors TLR7 and TLR9 have in this autoimmunity
  • Range of Autoimmunity Factors
    • are certain viruses and pathogens infecting B cells and using the machinery of these cells to create autoimmune conditions, continuing infection and immune dysfunction OR
      are pathogens, including Microbiota of bacteria which include L-form, biofilm, and intracellular bacterial forms infecting tissues, joints, bones, ligaments and causing immune system cells to react against these human tissues OR
      are pathogens which integrate and contain human tissue / cell markers causing an autoimmune reaction OR
      are pathogens mimicking human tissue / cell markers OR
      is human cell debris from oxidative stress and damage causing an autoimmune response OR
      do pathogens contain proteins or molecules which block immune response OR
      do pathogens contain similar proteins to that in surrounding human tissue OR
      are polymorphisms, mutations, predispositions, epigenetics, and changes in human genes from environmental factors and toxins causing autoimmunity

      Autoimmune factors found in ME / CFS patients may be arising from one or more of these dynamics, this area is the subject of ongoing research.


  • Novel new ways for addressing this problem through new or existing medical treatments. Can pathogens or their components and mechanisms be blocked (at pahtogen or host level) or inactivated or precisely targeted and destroyed and/or can vaccines be developed ?


(b)
ME is classified as a neuroligical illness and it has also been found to have significant immune system dysfunctions associated with pathogen infections. These pathogen infections have been found in the nervous system, and other body system and there is significant immune related inflammation and neurological inflammation. Investigate Viral, Bacteria, Lyme and Mycoplasma and other Pathogen infections of the nervous system, brain, intestines, blood, muscles, thyroid, liver, joints, organs, heart and blood vessels and immune system cells. Develop new and better tests over time.


(c)
A biological systems model needs to be developed through scientific trials, experiments and studies to

  • Why does Ampligen, an immune system modulating drug lead to improvements and recoveries in certain ME subgroups ? what are the biological and molecular pathways involved ?
  • identify all the abnormalities in the 2-5a synthetase / RnaseL anti-viral pathway & PKR pathway, and the causes of such whether by visues / mycoplasmas / other pathogens / bio-chemicals. Can this process be blocked or inactivated or reversed through medical drugs.
    Some of these have been deciphered here at: http://www.me-ireland.com/diag/3.htm#rn

  • map the relatioships between the the 2-5a synthetase / RnaseL anti-viral pathway and PKR pathway, STAT1 and other immune system subsets, the reactivation of latent endogenous viruses such as HERV-K18, the mitochondria and krebs cycle, and the methylation cycle blockages and the following :

    Viruses include: HHV6a virus, Herpes family viruses 1-8, Parvovirus B-19, CMV, Coxsackie viruses, Ross river virus, Q fever virus, Stealth virus, JHK virus,  Anellovirus, Parainfluenza Virus-5 (PIV-5), Paramyxovirus and measles viruses of the  Paramyxoviridae family, Cryptovirus, Borna virus, Enteroviruses in intestines, spinal fluids, nerve tissues, blood, brain, muscles. Retrovirus sequences found in 85% of ME cases, and Anellovirus found in 75% of ME cases in research conducted by Dr. Hornig and Dr. Lipkin in September 2013, but this will require further analysis. Most of these viruses listed here would include chronic, low level, sub-acute infections which inflict damage and immune activation, but which may not show up in standard or outdated tests.
    Reactivated latent viruses include HERV-K18, Varicella-Zoster virus, Herpes family viruses 1-8, measles viruses of the  Paramyxoviridae family
    Mycoplasma: M. fermentans, M. penumoniae, M. hominis, M. penetrans, M. pirum,  M. incognito. in intestines, spinal fluids, blood, brain, nerve tissues, muscles. These mycoplasmas would include chronic, low level, sub-acute infections which inflict damage and immune activation, but which may not show up in standard or outdated tests.
    Bacteria: Chronic Lyme disease, Ehrlichia, Bartonella, Brucella, Rickettsia, Chlamydia pneumonia, Staphylococcus spp. (live blood analysis), and Bacteria, including Microbiota of bacteria which include L-form, biofilm, and intracellular bacterial forms in spinal fluids, intestines, blood, brain, nerve tissues, muscles. Intestinal overgrowth of Gram positive D/L lactate-producing bacteria which are known to produce H2S (hydrogen sulfide) in the presence of certain heavy metals as a survival defense mechanism (Dr. Kenny De Meirleir). These bacteria would include chronic, low level, sub-acute infections which inflict damage and immune activation, but which may not show up in standard or outdated tests.
    Parasite: Cryptostrongylus pulmoni, Babesia, Candida, Giardia lamblia, Aspergillus Niger
    Molds, Bacteria and Mycotoxins in water damaged buildings: Stachybotrys family of molds, Cladosporium, Penicillium, Alternaria, Aspergillus, mycobacteria, Actinomycetes, Lipopolysaccharides (LPS), Microbial Volatile Organic Compounds (VOCs), Hemolysins. These can cause chronic inflammatory immune response and immune dysfunction over time.

    And novel new ways for addressing this problem through new or existing medical treatments. Can viral components and mechanisms be blocked (at viral or host level) or inactivated or precisely targeted and destroyed and/or can vaccines be developed ?

  • map the effects of elastase, cathepsin-G and m-calpain in fragmenting RnaseL. What causes this ? Can these processes be blocked, stopped or reversed ?
    Source: Interactions Between Rnase L Ankyrin-Like Domain and ABC Transporters as a Possible Origin for Pain, Ion Transport, CNS and Immune Disorders of Chronic Fatigue Immune Dysfunction Syndrome. Englebienne et al. 2001.
    Ribonuclease L proteolysis in peripheral blood mononuclear cells of chronic fatigue syndrome patients. J Biol Chem 2002 Jul 12; Demettre E, Bastide L, D'Haese A, De Smet K, De Meirleir K, Tiev KP, Englebienne P, Lebleu B.
    Chronic Fatigue Syndrome: Exercise Performance Related to Immune Dysfunction. Nijs et al. 2005

  • Fragment 1, an ankyrin binding repeat domain which is known to interact with various transport proteins. It is is capable of NF-kappaB mimicry. This may be interrupting the ion channels in the body.
    "these results show that upon pathological cleavage of RNase L, fragments containing the ankyrin domain are released, which could be capable of interacting with selected members of the human ABC superfamily, preventing their interaction with the normal cognate ankyrin protein and hence impairing their proper cellular function. This interaction constitutes a common physiological mechanism explaining numerous and currently unexplained symptoms experienced by patients with CFIDS, which are otherwise totally unrelated."
    Source: Interactions Between Rnase L Ankyrin-Like Domain and ABC Transporters as a Possible Origin for Pain, Ion Transport, CNS and Immune Disorders of Chronic Fatigue Immune Dysfunction Syndrome. Englebienne et al. 2001.
  • Is there a genetic cause of the abnormalities in the RnaseL anti-viral pathway and PKR pathway in ME ?


(d)
Abnormal Genes and Genetic Pathways


(e)
The role of VDR blockage on the immune system and it's vulnerability to viral, bacteria and other pathogen infections. Further testing and analyisis of the Marshall Protocol, and it's data on the VDR and pathogen infections, including Microbiota of bacteria which include L-form, biofilm, and intracellular bacterial forms. How VDR becomes blocked, the extent of blockage and the effects of such on Immunity. http://mpkb.org/home/diseases/cfs

(f) The role and effects of the MTHFR gene mutation found in some ME and CFS patients
The Human Genome Project found that this gene has been found to be mutated or abnormal in many people. Some ME and CFS patients have this genetic abnormality. This causes methylation cycle blockage, immune system abnormalities, including re-activation of latent viruses, thyroid and endocrine abnormalities, excess inflammation, antioxidant deficiencies, high homocysteine levels, arteriosclerosis and cardiac abnormalities, fatty liver, increased Cancer risk, neurotransmitter abnormalities and mood disorders, IBS, detoxification deficiency, multiple chemical sensitivity, cell growth and maintenance abnormalities. All of these are commonly found in most ME and CFS patients.
Testing Labs
- DNA Methylation Pathway with Methylation Pathway Analysis

Some more info
http://www.stopthethyroidmadness.com/mthfr/
Video Lecture by doctor
MTHFR Awareness

(g) A biological systems model needs to be developed through scientific trials, experiments and studies to

  • map the full range of immune system dysfunctions and immuno-deficiencies present ? and why are they present ? what are the subgroups ? what are the biological pathways involved ? what has caused or altered these pathways and what is maintaining this over time ? and how are these immune system dysfunctions related to each other and to nervous system dysfunctions ?
  • what is the part played by microglia in immune dysfunctions and autoimmunity ? what are the biological pathways involved ?
  • what role do endorphins have in immune dysfunctions and autoimmunity ? what are the biological pathways involved ?
  • what is the exact role played by toxins, inherited genes and genetic changes, and the dynamic between toxins and genes in the initiation of immune system dysfunctions ?

(h) The role played by Protein M in the immune dysfunctions in ME
Bacteria and other pathogens have evolved to use a protein called 'Protein M' to block all antibodies produced by the human immune system. This remarkable discovery by scientists at the Scripps Research Institute in 2014 sheds new light on chronic bacteria infections in humans. As many ME patients have chronic infections, this information is important. Tests are being developed for Protein M. See paper below
http://www.scripps.edu/news/press/2014/20140206lerner.html

  • Is Protein ME involved in the chronic infections in ME ?
  • Can Protein M be blocked or stopped by new medical drugs or new medical technologies ?
  • are other proteins, bio-chemicals and molecules being used by bacteria, viruses and other pathogens to block the antibody response or block other immune system activities ? If so, can these proteins, bio-chemicals and molecules be blocked or stopped ?

(i) The Lake Tahoe outbreak of the mid 1980's was a significant develpment in the history of ME /CFS, and has had a major impact on research, diagnostics and treatments worldwide. The medical findings presented by Dr. Cheney, Dr. Peterson and others to the CDC and Federal health bodies and scientific journals during and after the Lake Tahoe outbreak confirmed a rapidly spreading infectious disease with a short incubation period of one week or less. This narrows down the causative agent for the illness.

Some patients had HHV6a (then called HBLV), some had EBV, including reactivated EBV, some had CMV infection, and some had serious Herpes simplex infections. All of these particular infections have an incubation period of a few weeks, not one week. The exception to this being latent versions of these viruses which can be reactivated within a day or a few days, and certainly less than one week. Infection by bacteria, including brucella and other pathogens were also found in patients. Certain unusual immune system abnormalities and dysfunctions were found which undermined the body's ability to fight viruses and pathogens. These persisted over time. All this points to immune system damage and to acquired immune weaknesses and dysfunctions, which made patients more susceptible to viral infection and other opportunistic infections. The diagnosis of HHV6a was undermined by the fact that it was newly discovered and most doctors did not test for it and by outdated diagnostic technologies at the time which could not test for it. Enteroviruses, indicated in most ME epidemics throughout history, were not tested for in the Lake Tahoe epidemic. The medical and scientific findings of the Lake Tahoe epidemic need to analysed further by researchers to determine research priorities and directions.

(j) the scientific and medical findings of Dr. Garth Nicolson (USA) has consistently found that high percentages of ME patients have mycoplasma infections. A significant percentage also have co-infections including HHV6a and various bacteria infections. This correlates to illness severity. Dr. Nicolson also found evidence of immune dysfunctions. This ties into the work of other scientists and doctors who have consistently found viral, mycoplasma and other pathogen infections, along with immune dysfunction in ME patients.

  • What is the exact relationship between mycoplasma / viral / pathogen infections, both active and latent, and immune system dysfunction, including progression to chronic (long-term) inflammation ?
  • Research is showing that deep tissue infections and bone and cartilage infections and nerve system infections are playing a key role in some autoimmune illnesses, including some forms of arthritis. These infections are difficult to diagnose and find and many patients have been neglected. The immune system is attacking its own tissues, cells, cartilage, bone, nerves, etc. trying to get at viruses, bacteria, mycoplasma, pathogens, with resultant inflammation and serious damage over time.Inflamed tissue / cartilage suggests an immune response to something, that something is usually a pathogen though it could be a toxin or allergen in some cases. Also, mycoplasmas and viruses may be able to integrate host cell material into their own structures, thus initiating autoimmune responses by the immune system.

This will require deeper analysis of inflamed tissues, and the composition of mycoplasmas and viruses which are involved in an infection. Including identification of host cell material within mycoplasmas and viruses and reactions by immune system cells to this. The real challenge for medicine and science is to find the pathogen or toxin which initiates and perpetuates ME, and also causes a chronic inflammatory autoimmune and how it does this.

(k) reactivation of latent viruses in ME provide an added dimension to this complex illness. Are latent viruses hiding within immune system cells and other body cells producing chemicals which lead to chronic and excessive immune system activation, inflammation and damage to cells, tissues, nerves, myelin sheaths, cartilgage over time ? And can this be tracked and analysed in the nervous system, including the brain, CNS and ANS, the muscles, intestines and other body organs ? Does the recent research findings by Dr Ute-Christiane Meier in relation to MS and viruses have relevance to ME, considering the fact that both illnesses are classified as neurological, and involve immune system dysfunctions and infections ?

Association of innate immune activation with latent Epstein-Barr virus in active MS lesions.
Tzartos JS, Khan G, Vossenkamper A, Cruz-Sadaba M, Lonardi S, Sefia E, Meager A, Elia A, Middeldorp JM, Clemens M, Farrell PJ, Giovannoni G, Meier UC. Neurology. 2012 Jan 3;78(1):15-23.

Link between MS and latent viruses and inflammation (2012).Queen Mary University of London.

The following research paper outlines biological similarities between Multiple Sclerosis and ME/CFS. There are intriguing similarities. These areas need to be more fully researched.

Myalgic encephalomyelitis/chronic fatigue syndrome and encephalomyelitis disseminata/multiple sclerosis show remarkable levels of similarity in phenomenology and neuroimmune characteristics. Gerwyn Morris, Michael Maes. BMC Medicine 2013, 11:205 doi:10.1186/1741-7015-11-205

(l) Dr. John Chia's findings in relation to enterovirus infection of the intestines, muscles and nervous system needs to be replicated in order to establish what role enterovirus infection plays. Why do many patients with ME recover after treatment for enterovirus infection ? researchers will need to track infection biomarkers, immune system biomarkers, mitochondria and krebs cycle biomarkers, HPA axis biomarkers, and other biomarkers to establish how and why recovery takes place.

(m) The listing of immune system markers identified in the following pages need to be more fully investigated
www.me-ireland.com/diag/3.htm
www.me-ireland.com/scientific/1. immune.htm

(n) Which immune deficiencies and defects, mentioned below, play the major role in getting ME and in the chronic phase of the illness. See diagrams below.
In the first diagram below, the virus or other pathogen may be (a) exploiting an existing weakness in the immune system or genetic makeup of the person brought about by several environmental and genetic factors OR (b) creating certain weaknesses in the immune system, and these weaknesses persist over time and contribute to other immune system weaknesses and to opportunistic infections. The end result is chronic inflammation, infection, and continuing damage to cells, tissues and nerves, affecting many body parts, and causing deterioration of the patient.



Chronic Immune Dysfunction and Inflammatory State, Infection(s), Neurological, Endocrine, Mitochondria, and Oxidative Stress Cycles

(o) why are there low natural killer cells in ME patients ? why have the natural killer cells got abnormally low cytotoxicity ? why is the function of natural killer cells compromised ? are the natural killer cells being infected by viruses / mycoplasmas / pathogens ? is deficient ATP a factor ? how can these abnormalities be reversed or remedied ?

(p) Microbiome. Over 70% of immune system cells are located in the gastrointestinal tract. What are the gastrointestinal abnormalities and dysfunctions in ME patients and how do these problems cause the immune dysfunctions and inflammations typically found in ME patients ? what are the correlations between gut dysbiosis AND immune system functions AND inflammation, including neurological inflammation ? what immune subsets are involved ? what inflammation markers are involved ? what is the role of the vagus nerve in this ? How can these abnormalities be remedied / treated / reversed ?

(q) the role of genes from the microbial metagenome, and the sum total of their interactions with human cells and tissues over time in ME patients. Which microbes and which genes are involved ? and what are their individual and cumulative effects ? what are the effects on the immune system, the mitcohondria, cell functions, and body system functions in ME ?

(r) why is perforin low in ME patients ? how can this abnormality be reversed or remedied ?

(s) a biological systems model needs to be developed through scientific trials, experiments and studies to

  • map the mitochondria defects and krebs cycle and ATP defects in ME in the context of viral infections, mycoplasma and other infections, excessive immune system activation over time, oxidative stress, free radicals, and Nitric Oxide abnormalities, toxins, chemicals and heavy metals. Can these processes be blocked or inactivated or reversed through medical drugs and/or nutritional supplements ?
  • what is the exact role of the mitochondria in the immune system dysfunctions found in ME

(t) what is causing the reduced IgG subclass 1 and 3 found in ME and Fibromyalgia ? does it undermine the immune system so that it cannot control latent infections and fight active infections ? and does this lead to a reactivation of latent viruses ?

(u) why does Low dose Naltrexone work in many ME / CFS cases and in other autoimmune diseases ? what are the exact biological pathways involved ? and what is the part played by microglia in immune system dysfunction ?

(v) A biological systems model needs to be developed to establish the role of Cryptostrongylus pulmoni infection of the body and accompanying immune system dysfunction. And novel new ways for addressing this problem through new or existing medical treatments. Can parasite components and mechanisms be blocked (at viral or host level) or inactivated or precisely targeted and destroyed and/or can vaccines be developed ?

(w) Applications of Immuno therapy: This usually involves extracting and then re-training / re-programming / restructuring various subsets of live immune cells (NK cells, Lymphocytes, T-cells, B-cells, Macrophages, Cytokines) and then injecting them back into the body. Studies show it is effective in some Cancers and chronic illnesses.
Other therapies involve using bacteria / virus / antigens to stimulate immune response or destroy another pathogen / tumour. Some topical creams can powerfully stimulate immune system components and subsets of immune cells.
How can we improve the precision and acuracy of Immuno therapy in ME / CFS patients ?

(x) Some medical drugs and supplements mentioned in the following link should be investigated further - www.me-ireland.com/treat/3.htm


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(iii) Infection of the nervous system and toxin induced damage to the nervous system with resultant central and autonomic nervous system dysfunctions

 

 


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