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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

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. The severe inflammation of the spinal cord, indicated an infection, by a virus or other pathogen. 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 psychiatrists and doctors.

There was another case of an ME patient in England who had serious enteroviral infection of the brain and nervous system and he was told by doctors that he was suffering from depression. He was given psychiatric drugs which made him worse. This neglect by doctors made him very ill and he deteriorated rapidly. He committed suicide. An autopsy revealed that he had serious enterovirus infection of the brain and nervous system. Read article here - https://listserv.nodak.edu/cgi-bin/wa.exe?A2=ind0112a&L=co-cure&F=&S=&P=62

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.

"an agent was repeatedly transmitted to monkeys from two patients (Pellew and Miles, 1955). When the monkeys were killed minute red spots were observed along the course of the sciatic nerves. Microscopically infiltration of nerve roots with lymphocytes and mononuclear cells was seen and some of the nerve fibres showed patchy damage to the myelin sheaths and axon swellings. Similar findings had been produced by the transmission of an agent to monkeys from a child with poliomyelitis in Boston, Massachusetts, in 1947 (Pappenheimer, Cheever and Daniels, 1951). However, in these monkeys the changes were more widespread, involving the dorsal root ganglia, cervical and lumbar nerve roots and peripheral nerves. Perivascular collars of lymphocytes and plasma cells were seen in the cerebral cortex, brain stem and cerebellum, spinal cord and around blood vessels to the nerve roots. There was no evidence of damage to the nerve cells in the brain or spinal cord. The distribution and intensity of the lesions varied considerably from monkey to monkey. This patho- logical picture of mild diffuse changes corresponds closely to what might be expected from clinical observations of patients with neurological involvement in epidemic Neuromyasthenia
Parish JG (1978), Early outbreaks of 'epidemic neuromyasthenia', Postgraduate Medical Journal, Nov;54(637):711-7, PMID: 370810.

The evidence for viral infections of the nervous system and other body parts is presented in Viral infections section

Many patients have been told they have no virus / pathogen infection, when they actually have an infection which cannot be detected in simple blood samples or through use of outdated diagnostic equipment. This has created an 'Epidemic of Misdiagnosis'. Yet ignoring these infections can lead to chronic degenerative illness and long-term disability with costs to the individual, the family and national economy. 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.

In ME, specific viruses are infecting the nervous system, and causing accompanying inflammation of nerve tissue and brain tissue. Toxins such as heavy metals, organophosphates, chemicals and pollutants have been found in many ME patients, and these toxins cause significant damage to the nervous system and the immune system over time. The immune system is in a dysfunctional pro-inflammatory, activated state, as evidenced by the shift to TH2 inflammatory cyokine dominance in ME, and other immune markers, and these all suggest infection. This has been confirmed in several research studies, which are catalogued in the Scientific Evidence section. Autopsy evidence presented at the Royal Society of Medicine meeting in the series “Medicine and me” on 11th July 2009 by Dr Abhijit Chaudhuri, showed slides of inflammation of the dorsal root ganglia in three ME patients.

During the ME outbreak in Iceland in 1947-48, there were many cases of diffuse brain and CNS injury, and neurological inflammation and dysfunctions. Some people even developed Parkinson's Disease type symptoms and died

"Three children from this epidemic in the town of Friedrickshavn, became moribund and were unable to leave their beds, they eventually died of Parkinson's-like illness and were autopsied. Parkinson's Disease is almost unheard of in children. There can be no doubt that we were dealing with a diffuse inflammatory brain injury and at least some of these cases, involved the basal ganglia"
Source: A Brief History of Myalgic Encephalomyelitis by Dr. Byron Hyde

The particular viruses which are consistently found in ME such as HHV6a, the Herpes family 1-8, Parvovirus B19, Stealth virus, Enteroviruses have a tendency to infect the nervous system and the brain. Recently the Herpes family viruses have been found to reactivate dormant endogenuous viruses (which humans inherit at birth) and these reactivated viruses are also believed to infect the nervous system and trigger strong immune responses. These infections are causing inflammation in the nervous system and are most likely responsible for the brain lesions and brain hypo-perfusion and cognitive dysfunctions consistently seen in most ME patients. Mycoplasma which has also been found in many ME patients is also capable of infecting the nervous system and brain and may be a co-factor in the illness.

Dorsal root ganglia inflammation and dysfunction and sympathetic nervous system dysfunction are emerging as very important factors in ME according to recent genetic research by Dr. Light and her research team in Utah, USA. These are key aspects of the nervous system and an infection, inflammation and dysfunction in these centres has multiple domino effects on other systems in the body. It is highly probable that this is the result of infection and/or damage caused by inflammatory cytokines resulting from immune over-activation and autoimmunity. This is being unravelled by scientific research. Importantly, sympathetic nervous system dysfunction can lead to impaired blood flow and metabolite removal (after exercise) from muscles and tissues, and resultant stress on mitochondria, krebs cycle and antioxidant systems as proposed by Dr. Light and her research team. Continuing Genetic studies by Dr. Light are shedding further light on this.

The clinical findings of Dr. Jay Golstein in California indicate that there are neurological "gating" deficits in ME patients. His book Betrayal by the Brain: The Neurologic Basis of Chronic Fatigue Syndrome, Fibromyalgia Syndrome, and Related Neural Network Disorders (The Haworth ... networks in health & illness) details the many neurological abnormalities and dysfunctions in ME patients. It is believed that these neurological dysfunctions are caused by inflammation of the nervous system. Scientific research suggests this may be caused by infection and inflammatory cytokine damage or oxidative stress or mitochondria dysfunction. The research and clinical findings show that there is a shift to excess glutamate production and activity and excess NMDA activity in the brain and nervous system, and a deficiency of GABA. This causes neuro-excitability and neurotoxicity, which explains the sleep problems, irritability, mood changes, brain fog, autonomic dysfunctions, and many cognitive dysfunctions found in ME .

Abnormal spinal fluid proteomes in ME found by Baraniuk and Schutzer point to inflammation or infection and / or central nervous system dysregulation. This confirms many of the findings mentioned above.

Viral infections of the nervous system produce a very wide range of symptoms over time. The onus is on doctors, consultants, hospitals and researchers to carry out more thorough, detailed and precise diagnostics to identify these neurological infections.

Research Priorities

The following scientific research needs to be undertaken to clarify the situation:

(a)

The research so far, shows:

  • infections are occurring in the brains and nervous system of subgroups of CFS patients.
  • infections of the immune system is occurring. These include mycoplasma, lyme, viruses, bacteria.
  • the immune system is inflicting inflammatory damage in the brain and nervous system
  • abnormal microglia activation which suggests infection
  • infections of the red blood cells is occurring, and this is causing these cells to form abnormal shapes. This is affecting the delivery of oxygen and nutrients to the brain cells. This can cause the death of brain cells and neurons

    Evidence: www.me-ireland.com/listing.htm and www.me-ireland.com/scientific.htm

    These factors can cause the motor cortex, the frontal cortex, the basal ganglia, the dorsal root, limbic system, thalamus, anterior cingulate cortex to malfunction or function poorly. This has multiple domino effects on the body.
    The above factors need to be investigated by scientific researchers

(b)

  • Test spinal fluids, inflamed or infected intestinal tissue and muscle tissue, B-cells, and inflamed samples from dorsal root ganglia, basal ganglia, brain stem, vagus nerve, spinal cord, cervical and lumbar nerve roots and peripheral nerves and sites of brain lesions and sites of brain lesions for the following viruses and pathogens. This includes latent, partially latent and new chromonsonally integrated pathogens.
  • MRI scans and Spectroscopic signature and EMF signature scans may be able to detect localized infections of the nervous system.
  • New genetic sequencing devices can rapidly identify the genetic signatures of viruses and other pathogens, these would be recommended as they improve accuracy, while reducing time and cost.

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 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.

(c) A biological systems model needs to be developed for :
- investigate the role of viruses / mycoplasmas / lyme and other pathogens in the spinal fluids, intestinal tissue, inflamed muscle tissue, blood IgM and IgG and other blood subsets and blood plasma, B-cells, and inflamed samples from dorsal root ganglia, basal ganglia, brain stem, vagus nerve, cervical and lumbar nerve roots and peripheral nerves and brain in ME patients. Concentrating on areas of acute, sub acute and chronic inflammations.

- the role of nervous system infection and accompanying immune system reactions leading to inflammation of nerve tissue, damage / destruction of nerve tissue, nerve receptors, neurotransmitter levels, and the set of autoimmune factors and immune dysfunctions factors involved. And novel new ways for addressing these problems through new or existing medical treatments. Can this be blocked (at viral or host level) or inactivated or precisely targeted and destroyed and/or can vaccines be developed ?

- secondary effects, such as sympathetic nervous system involvement and relationship to impaired blood flow and metabolite removal (after exercise) from muscles and tissues, and resultant stress on mitochondria, krebs cycle and antioxidant systems, HPA axis involvement, methylation cycle involvement, autonomic system involvement, orthostatic intolerance and POTS involvement. And novel new ways for addressing this problem through new or existing medical treatments. Can abnormalities and dysfunctions be blocked or inactivated or precisely targeted and destroyed and/or can vaccines be developed ?

(d) establish how this leads to neurological "gating" deficits, as outlined by Dr. Jay Goldstein. And novel new ways for addressing this problem through new or existing medical treatments. Can these mechanisms be blocked (at viral or host level) or inactivated or precisely targeted and destroyed and/or can vaccines be developed ?


(iv)
Mitochondria and krebs cycle dysfunctions

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

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

Cardiomyopathy arising from mitochondria dysfunction, oxidative stress and infections

The evidence presented in our Scientific Evidence section suggests that the mitochondria are being destroyed and the krebs cycle is being disrupted in ME patients. This has very serious consequences. The research indicates the mitochondria are being stressed / destroyed by oxidative stress factors including virus / mycoplasma / pathogen infections, an immune system which is in a chronic activated and dysfunctional state and is chronically fighting infections and producing free radicals and inflammation, and toxins organophosphates, chronic emotional / mental stress, chronic allergy, poor nutrition, which are further increasing this oxidative stress load. This was first postulated by De Freitas and Behan in the early 1990's. This has been developed further by Dr. Martin Pall through his NOS and peroxynitrite research studies showing several types of oxidative stress factors in ME , which causes severe damage to mitochondria and the krebs cycle over time ( Explaining 'Unexplained Illnesses': Disease Paradigm for Chronic Fatigue Syndrome, Multiple Chemical Sensitivity, Fibromyalgia, Post-Traumatic Stress Disorder, and Gulf War Syndrome ). Both the mitochondria membrane and mitochondria DNA have been found to be damaged, and the electron transport chain enzymes are defective in ME and Fibromyalgia. Mitochondria damage and Krebs cycle dysfunctions interfere with immune system function, causing immune dysfunctions and possibly some types of autoimmunity. ATP, mitochondria and Krebs cycle are involved in energy production throughout the body and affect every gland, organ and system in the body, and some leading doctors believe this dysfunction in the krebs cycle lies at the root of ME and many other illnesses involving fatigue. This is the subject of ongoing scientific research worlwide, in particular the relationship of mitochondria and the krebs cycle to immune system function.

Furthermore, the mitochondria and krebs require essential nutrients, minerals, biochemicals, methylation end-products, and glutathione in order to function effectively AND they are also susceptible to disruption / attack by pathogens or free radicals or environmental toxins or excess metabolites (from exercise) and deprivation of the aforementioned essential nutrients. Scientific research will need to focus on these important factors. Dr. Edward Conley who runs the famous Fatigue, Fibromyalgia and Autoimmune Clinic, Michigan, USA  has publically stated that solving the ATP, mitochondria and krebs cycle problems in ME resolves the ME illness. His medical clinic has successfully treated thousands of ME patients.

Research Priorities

The following scientific research needs to be undertaken to clarify the situation:

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

- the exact nature of mitochondria dysfunction and destruction in ME with some emphasis on damage to mitochondria membrane and mitochondria DNA, and defects in the electron transport chain enzymes. The activities of the mitochondria and krebs cycle in ME patients will need to studied in real time. Every aspect will need to be examined and analysed. If possible, during exercise when the mitochondria and krebs cycle of ME patients are put under severe strain. And there is rapid build up of lactic acid levels which abnormally persists over time. These biological mechanisms must be deciphered and understood in detail.

- why is there mpaired Oxidative Phosphorylation in ME patients ? what is causing it ? What mechanisms are involved and how can they be stoppped, blocked or protected against ?

- how oxidative stress factors including virus / mycoplasma / pathogen infections, an immune system which is in a chronic activated and dysfunctional state and is chronically fighting infections and producing free radicals and inflammation, and toxins organophosphates, chronic emotional / mental stress, chronic allergy, poor nutrition are increasing this oxidative stress load on the mitochondria. What mechanisms are involved and how can they be stopped, blocked or protected against ?

- establish the domino effects of mitochondria damage and krebs cycle dysfunction on the immune system functions and signalling.

(b) Another biological model needs to be developed to assess the
- effects of cell membrane damage and mitochondria membrane damage on the production of free radical-induced cytokines which cause inflammation, pain, increased sensitivity, dizziness and a worsening of the illness.
- assess and evaluate if the essential nutrients, minerals, biochemicals, methylation end-products, and glutathione are being produced / provided in order for mitochondria and krebs cycle to function normally and effectively in ME pateints AND if excess metabolites (from exercise) are implicated in any dysfunctions. If so, this needs to be expanded to examine the domino effects on the immune system and immune system function and signalling.
- the effects of malabsorption of important nutrients in the intestines, digestive enzyme deficiencies in the intestines, malabsorption in the intestines due to structural problems or digestive performance problems resulting from diseases of the intestines, hypochlorydia, failure to absorb B vitamins and certain minerals such as magnesium, copper, zinc, manganese and selenium on (i) Krebs cycle, mitochondria (ii) antioxidant functions and status (iii) and Methylation cycle (iv) immune system function


(c)
re-activation of latent viruses, HERV's including HERV-K18, and Herpes viruses

There is some research which indicates that EBV virus and HHV6a virus activates a latent virus, HERV-K18, which all humans inherit and is part of the human genetic makeup. This is important as both EBV virus and HHV6a virus are consistently found in many ME patients. This activation of a latent virus, HERV-K18, only happens in certain people, and it is believed that this may be cause of ME or a co-factor in ME. The reactivated virus HERV-K18 enocodes a superantigen which causes strong immune activation and immune dysfunction, inflammation and it hides in B-cells.

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 vivo 27: 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.

The medical findings presented by Dr. Cheney and Dr. Peterson to the CDC after the Lake Tahoe outbreak in the mid 1980's confirmed virus infection, in particular HHV6a virus infection (then called HBLV but later renamed HHV6a) and accompanying reactivation of latent Epstein Barr virus in some patients. This was accompanied by immune dysfunctions and infections by other pathogens, including bacteria. Some of these patients went on to develop Cancers.

Research Priorities

The following scientific research needs to be undertaken to clarify the situation:

(a) A biological systems model needs to be developed through scientific trials, experiments and studies to establish the extent of HERV re-activation and infection in ME . The effects of this on all subsets of the immune system. The effects of this on the nervous system, the mitochondria and HPA axis. Can components and mechanisms be blocked (at viral / pathogen or host level) or inactivated or precisely targeted and destroyed and/or can vaccines be developed ?

(b) How are latent Herpes viruses being reactivated in ME ? what biological pathways are involved ? Can components and mechanisms be blocked (at viral / pathogen or host level) or inactivated or precisely targeted and destroyed and/or can vaccines be developed ?

(c) 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 ?

(d) Are Methylation cycle blocks and methylation failure undermining and weakening immune system function to the point that latent viruses can become active again in ME patients ?


(vi)
Idiopathic CD4+ T lymphocytopenia

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. The involvement of other viruses and toxins have been proposed in this illness. Click here to view some scientific studies into this illness. Further scientific research will be required to establish if they are the same illness or if Idiopathic CD4+ T lymphocytopenia is a subgroup of ME or if they are different illnesses which are similar in some respects. This is important in the context of causative factors, structure of causation and the perpetuating factors in the illness.

Research Priorities

The following scientific research needs to be undertaken to clarify the situation:

(a) A biological systems model needs to be developed through scientific trials, experiments and studies to establish the biological mechanisms of CD4+ T lymphocytopenia and the involvement of viruses and other pathogens. If it is a subgroup of ME or a separate illness. How this relates to immune system dysfunction. And novel new ways for addressing this problem through new or existing medical treatments. Can components and mechanisms be blocked (at viral / pathogen or host level) or inactivated or precisely targeted and destroyed and/or can vaccines be developed ?


(vii)
Toxic build up in the body. Organophosphate toxicity, heavy metal toxicity, mycotoxins

Cumulative toxin load is important over time prior to ME onset and after ME onset, especially in cases of impaired detoxification. There is evidence of toxic build up in the body of mst ME patients. Flow reversal in the liver and the brain has been found in over 90% of ME patients. Chronic Cerbral Spinal Venous Insufficiency (CCSVI). Chronic Hepatic Venous Insufficiency (CHVI). Cardiac Dysfunction. This reversal leads to auto-intoxication and a build up of toxins and toxin related damage to cells and tissues with serious effects for the patient over time. Cardiac dysfunction is believed to play a key role in this flow reversal.

Video Lectures by Dr. Cheney on Flow Reversal in Liver and Flow Reversal in Brain

A toxin or toxins have been cited in research and clinical findings as trigger mechanisms for ME. Diagnostic tests in certain clinics have revealed excessive build-up of toxins in many ME patients. Research has revealed that there is an average of 140 toxic chemicals, heavy metals and pollutants in the human body. Research also shows that there are 200 toxic chemicals, heavy metals and pollutants in the umbilical cord of babies when they are born. Since 1945 there has been a massive increase in environmental toxins which has found it's way into human food, water, liquids, air and human bodies, and there has been an accompanying increase in toxin related illnesses such as Cancer and autoimmune diseases, including ME and Fibromyalgia. These disturbing facts and the scientific evidence are detailed in the book The Autoimmune Epidemic By Donna Jackson Nakazawa (Touchstone. 2009) and in Dr. Noel Rose's excellent book The Autoimmune Diseases . It is known that toxins can damage mitochondria and interfere with the Krebs cycle, and also interfere with neurological, endocrine and immune system functions and with the genes. These are the main problems in ME.

A number of peer-reviewed scientific studies have shown a causal link between non-Hodgkin lymphoma and exposure to PCBs, sewage sludge and other toxins. This may have relevance to the increased risk of Lymphomas and certain Cancers in ME.

There is evidence of flow reversal in the liver and the brain, Chronic Cerbral Spinal Venous Insufficiency (CCSVI), Chronic Hepatic Venous Insufficiency (CHVI) and Cardiac Dysfunction in most ME patients. This reversal leads to auto-intoxication and a build up of toxins and toxin related damage to cells and tissues with serious effects for the patient over time. Cardiac dysfunction is believed to play a key role. There are interesting video lectures by Dr. Cheney on this subject below.
Video Lectures by Dr. Cheney on Flow Reversal in Liver and Flow Reversal in Brain

Environmental toxins play a role in the initiation and perpetuation of several diseases and illnesses, and in genetic mutations. This is widely accepted as a scientific and medical fact. And it is the subject of ongoing research worldwide. Gulf War Illness shares many biological similarities with ME. In some cases people with Gulf War Illness were even diagnosed with ME. It has been established through scientific research that Gulf War Illness was caused by a combination of exposure to depleted uranium in exploded shells, and to the biological warfare agents which were released into the air through bombing of Iraqi chemical and biological weapons sites and to adverse reactions to anti-nerve gas tablets, and the multiple vaccines given to soldiers during the first Gulf war in 1991. The gulf war in 1991 was the first war where western soldiers were directly and indirectly subjected to multiple toxins and chemicals. These toxins and chemicals caused various biological dysfunctions and abnormalities and susceptibility to infections, genetic mutations and birth defects in offspring, and Cancers in soldiers which lasted for many years after the gulf war. Much of this scientific and medical evidence was ignored. Yet psychiatrists were hired by the military and by governments to wrongly claim that it was a psychiatric illness and "all in the mind", a somatic syndrome. This mis-diagnosis led to the deaths and severe suffering of many ex-soldiers. Unfortunately this has occurred in other illnesses and diseases.

Research Priorities

The following scientific research needs to be undertaken to clarify the situation:

(a) A biological systems model needs to be developed through scientific trials, experiments and studies to establish the effects of different toxins, heavy metals, PCB's, and organophosphates on the 2-5a synthetase / RnaseL anti-viral pathway and PKR pathway, and other immune system subsets, and on autoimmunity, Lymphoma and Cancer probability, ATP, mitochondria and krebs cycle, the methylation cycle, the Hypothalmus and HPA axis and gene expression. And novel new ways for addressing this problem through new or existing medical treatments. Can toxin components and mechanisms be blocked (at toxin or host level) or inactivated or precisely targeted and removed and/or can more effective detoxification methods be developed ?


(viii)
Excessive chronic stress over time and HPA axis dysfunction and accompanying immune system dysfunction

excessive stress levels over a prolonged period of time, combined with inadequate sleep or sleep deprivation which has adverse effects on HPA axis function, the immune system and susceptibility to infections, individual gland functions and structures, cortisol production, glucocorticoid production and it's effects on immune system function, neurological function and the relationships between all of these functions. Life in the 21st century has become more stressful due to globalisation of business and increased competition between people, the Internet and new technologies which operate 24 hours a day, 7 days a week, the existence of a high and almost constant state of arousal in the general population, the massive financial speculative bubbles followed by crashes and deep economic recessions, the government austerity policies and economic depressions, the stress of living in this type of economic environment and having to "keep up with the Joneses" or suffer stigma and prejudice for not doing so, the continued widspread pollution of the environment which affects food, water and air and the stresses that this creates, the breakdown of traditional family structures and community structures and voluntary support structures which gave people a sense of belonging, dignity, and respect, etc., etc. Prolonged stress and sleep deprivation, often accompanied by poor nutrition, and accompanying chronic adrenal stress and adrenal exhaustion and it's negative effects on the thyroid gland and it's hormones, may be contibuting to the abnormal production of Reverse T3 in ME. Research and the clinical findings of doctors strongly suggests Reverse T3 is being over-produced and reaching excessive levels in the bodies of ME patients. This is being postulated as a cause of ME in most if not all cases by leading medical doctors and scientific researchers in the field.

Excessive stress can cause a near constant 'fight or flight' response, putting pressure on the adrenal glands and HPA axis. If this is chronic, the fight or flight response can cause the body to shut down or slow down some functions in order to survive, this 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. This has a domino effect on immune function and HPA axis functions. Many scientific studies have found that excessive stress lies at the root of many Cancers, heart attacks, strokes, diabetes, and other physical illnesses. Science has proved that excessive cortisol (from too much stress or fight and flight responses) over prolonged periods of time has been found to cause immune system dysfunctions and abnormalities, including a shift to TH2 inflammatory cytokine dominance in the immune system. This has been consistently found in ME patients. Furthermore, studies have shown shrunken adrenal glands in ME patients, this indicates excessive strain on the adrenal glands over time, resulting from chronic stress, chronic allergies, or pathogen infections. Dr. Edward Conley (Michigan, USA) has stated that adrenal gland and hormone abnormalities are consistently found in many ME patients. The new branches of science known as Neuroendocrine Immunology and Neuroimmunology have great relevance to ME as they are making great scientific advances in unravelling the complex relationships and interactions between the endocrine system and neurological system and immune system, and oultining how biological systems fit together in the human body. Science is unravelling the adverse biological and biomedical effects of chronic and excessive stress, sleep deprivation, chronic adrenal stress and exhausation and "burn-out" over extended periods of time on the immune system, thyroid gland, HPA axis, brain and other body systems.

Research Priorities

The following scientific research needs to be undertaken to clarify the situation:

(a) A biological systems model needs to be developed through scientific trials, experiments and studies to establish all of the effects of chronic stress and sleep deprivation over several months or years and accompanying chronic adrenal stress and exhaustion on (i) the adrenal gland itself (ii) the thyroid gland (iii) the hypothalmus gland and Pituitary gland and their functons and interactions with other glands (iv) cellular uptake of glucose, oxygen and nutrients AND the effects of all these aforementioned factors on (i) the 2-5a synthetase / RnaseL anti-viral pathway and PKR pathway, and other immune system subsets, and on autoimmunity (ii) Lymphoma and Cancer probability (iii) ATP, mitochondria and krebs cycle (iv) the methylation cycle (v) HPA axis and (vi) gene expression. And novel new ways for addressing this problem through new or existing medical treatments. Can these abnormal / dysfunctional processes be reversed or normalised through medication, diet and lifestyle changes and other treatments ?


(ix)
Inherent Immunity weaknesses

The famous last words of Louis Pasteur, the great scientist, on his deathbed stating "The pathogen is nothing, the terrain is everything "  shows the importance of one's immune system, general health, diet and lifestyle and inherited genetic weaknesses and strengths. Not everybody gets ME even though they are exposed to and infected with the same viruses and pathogens as the people who get ME. There is some scientific evidence to suggest that immune system depletion and weaknesses, genetic weaknesses, bowel toxicity, excessive stress, malnutrition (poor diet), sleep deprivation and environmental toxins play a part in makng a person's immune system susceptible to infection and diseases. It is a well established fact that malnutrition can cause people to become more susceptible to viral, bacteria and other infections and accompanying diseases, and that alcoholism, drug dependence, and smoking can cause people to become susceptible to certain diseases, and that exposure to certain toxins can cause people to become more susceptible to certain toxin-related diseases. In all such cases the immune system is weaknened and compromised. This is important in ME, and both initial causes and predisposing factors will need to examined.

Scientific research is gradually revealing that immune systems can be enhanced, extended, "trained" or "programmed" to destroy different categories of pathogens. This fact was first established widely by Dr. Edward Jenner in the 18th century. Some recent research funded by The National Institutes for Health (NIH) in the USA, has found that it is possible to re-educate certain parts of the immune system to not attack human tissue and human cells. The preliminary findings are promising and if replicated could form the basis of revolutionary new medicines to effectively treat all autoimmune diseases - Read article by clicking here

Scientists at The Scripps Research Institute have identified the molecular pathways and mechanisms involved in Lupus, an autoimmune disease and developed re-engineered cells to block the development of Lupus and are now investigating drugs with similar blocking mechanisms. Read article by clicking here.

Research Priorities

The following scientific research needs to be undertaken to clarify the situation:

(a) a biological systems model needs to be developed through scientific trials, experiments and studies to establish if immune systems in ME and other autoimmune illnesses can be enhanced, re-trained, re-programmed, re-configured, re-patterned to (a) destroy different categories of pathogens (b) correct immune system weaknesses, deficiencies and dysfunctions (c) not attack human tissue, cells, and organs. And novel new ways for addressing this problem through new medical / scientific treatments. Do the the findings of the autoimmune research funded by the NIH and the Scripps Research Institute mentioned above have applications to ME and its immune system abnormalities ?

(b) Investigate which immune system markers are turned on or off in ME, and can they be changed to bring about improvements / recovery ? Which immune signalling systems and targeting systems are involved in ME and can they be changed to bring about improvements / recovery ? what immune cell cytoxic activities are deficient in ME and can they be changed to bring about improvements / recovery ?


(x)
Lymphatic Drainage

The findings of Dr. Perrin (The Perrin Clinic) in relation to lymph system dysfunction and sympathetic nervous system dysfunction, in ME may correlate to the findings of Dr. Light and her research team in the USA. The combination of lymph system dysfunction and sympathetic nervous system dysfunction would explain immune system dysfunctions, neurological dysfunctions and endocrine dysfunctions, exercise intolerance, rapid lactic acid build up, the gradual build up of toxicity, and oxidative stress, all of which are found in ME patients. This merits further scientific research, including cross-discipline and cross-field studies, and the development of a coherent biological systems model to explain the causes and domino effects of these two dysfunctions.

Research Priorities

The following scientific research needs to be undertaken to clarify the situation:

(a) biological systems model needs to be developed through scientific trials, experiments and studies to identify the specific lymphatic drainage and dysfunctions present in ME . And if identified, establish the causes of this dysfunction, whether viral or toxin induced or metabolism induced, and the exact effects on immune system functions and autoimmune risks.


(xi)
Blocks in the Methylation cycle

A recent research finding suggests that blocks in the methylation cycle and a deficiency of glutathione may lead to insufficent methylation and immune system function and to the re-activation of latent, endogeneous viruses in the human body. These latent, endogeneous viruses are inherited from parents and lie dormant in healthy people, but can be re-activated by certain factors. It is believed that insufficent methylation may be one of these factors. The immune system is dependent on methylation for it's functions and effectiveness, and defects in methylation has adverse effects on immune system function. Whether this is the root cause of ME or the result of ME has yet to be established. This is the subject of continuing research by top scientific researchers.

Research Priorities

The following scientific research needs to be undertaken to clarify the situation:

(a) a biological systems model needs to be developed through scientific trials, experiments and studies to establish the causes, exact mechanisms and the effects of methylation cycle blocks in ME and its effects on immune system weaknesses, deficiencies and dysfunctions and inability to fight viruses and pathogens, including latent viruses and pathogens. And novel new ways for addressing this problem through new or existing medical treatments.


(xii)
Intestinal dysfunction and poor absorption of key vitamins and minerals involved in the Krebs cycle and immunity

intestinal dysbiosis and excessive producton of bowel toxins (excessive hydrogen sulphide, excessive toxins from candida and/or bad bacteria) AND possible interactions of toxins with heavy metals. Cumulative toxic load is important over time prior to ME onset.

Research Priorities

The following scientific research needs to be undertaken to clarify the situation:

(a) a biological systems model needs to be developed through scientific trials, experiments and studies to establish
- the effects of intestinal dysbiosis and interactions with heavy metals, organophosphates and toxins on the immune system, autoimmune risk factors and inability to fight viruses and pathogens, including latent viruses and pathogens. And novel new ways for addressing this problem through new or existing medical treatments.
- the effects of malabsorption of important nutrients in the intestines, digestive enzyme deficiencies in the intestines, malabsorption in the intestines due to structural problems or digestive performance problems resulting from diseases of the intestines, hypochlorydia, failure to absorb B vitamins and certain minerals such as magnesium, copper, zinc, manganese and selenium on (i) Krebs cycle, mitochondria (ii) antioxidant functions and status (iii) and Methylation cycle (iv) immune system function
- magnesium blockage at intestinal and/or cellular level or Krebs cycle level / ATP level

(xiii)
Fibromyalgia

The scientific findings mentioned on www.me-ireland.com/diag/fibro.htm need to be replicated and analysed further to decipher the biological causes of Fibromyalgia. Subgroups need to be identified.

(xiv) Excessive production of free radicals and their effects on the mitochondria, immune system, heart and blood vessels

excessive production of free radicals and oxidative stress from environmental toxins and dysfunctional detoxification and antioxidant mechanisms and overactive and dysfunctional immune system fighting infections. Causative mechanisms for free radical generation would be important to investigate further.

Research Priorities

The following scientific research needs to be undertaken to clarify the situation:

(a) a biological systems model needs to be developed through scientific trials, experiments and studies to confirm
- The oxidative stress cycle, involving Nitric oxide and Peroxynitrite proposed by Dr. Martin Pall needs to be confirmed in more studies. In particualr the effects on mitochondria, immune system, heart and blood vessels of ME patients


(xv) Allergies and chronic immune inflammatory system activation

chronic allergic response from continuous exposure to environmental allergens eg. dust, moulds, mites, pollen, etc. which causes chronic immune system activation over a prolonged period of time. It also causes chronic arenal gland activation and cortisol production over time. Some scientific studies have shown shrunken adrenal glands in ME patients, this indicates excessive strain on the adrenal glands over time, resulting from chronic stress, chronic allergies, or pathogen infections. This chronic allergic activation may lead to immune system and adrenal gland exhaustion, burn-out, and dysfunctions.

Research Priorities

The following scientific research needs to be undertaken to clarify the situation:

(a) a biological systems model needs to be developed through scientific trials, experiments and studies to confirm
- the scientific findings of Dr. Shoemaker in relation to sick building syndrome, mycotoxins and molds in ME. See Section Environmental Toxins, Heavy Metals, Organophosphates


Putting it all Together

The ATP, mitochondria & Krebs cycle dysfunction and abnormalities and fall in ATP production are the most serious disorder. This is being caused by one or more of the following - infection, a toxin, a prolonged stress response over time, excessive oxidative stress and free radicals, a genetic weakness, or some interaction between environmental toxins and genes. Mitochondria and krebs cycle dysfunction lies at the heart of the energy deficit and fatigue of ME. For example, the immune system is a significant user of ATP. A chronically activated immune system uses up a large proportion of total ATP. And if this ATP production is under-peforming, then there is less ATP being produced and other body processes will have less ATP and thus less energy. The end result is less energy for effective immune function and other bodily processes and the total exhausation of the patient. At the same time the mitochondria are being put under severe stress, as a chronic virus infection(s) can cause excessive immune activation, inflammation and oxidative stress in the body and the resultant free radicals can destroy mitochondria and interrupt the krebs cycle, lowering ATP production, and this turn weakens the immune system further. This occurs at a time when extra demands are being made on the mitochondria and ATP to help the immune system fight infection. The disturbed Nitric Oxide cycle described by Dr. Martin Pall would apply here, enhancing oxidative stress damage to the body. Thus a cycle is established of lower energy, lower ATP, damaged mitochondria, a weakened immune system, oxidative stress which persists over a long time and the accumulation of damage to organs and the body over time.

The blocks in the methylation cycle and deficiency in glutathione also affects most biological and metabolic processes in the body, and also causes fatigue. Over time, these dysfunctions can lead to other dysfunctions and abnormalities. The two aforementioned dysfunctions combined with the dysfunctional 2-5a synthetase / RnaseL anti-viral pathway and HPA axis lead on to serious immune system malfunction, involving several types of immune system cells. It adversely affects immune cell numbers, functions, performance and mobility, and cell apoptosis. There is a shift to TH2 cytokine dominance in the immune system and an increase in TNF-a activity both of which are pro-inflammation. This contributes to an increase in inflammation and pain, and the development or worsening of allergies, rhinitis, hay fever and sinus problems. This immune shift also leaves the body vulnerable to viral infections and some types of bacteria, chlamydia and mycoplasma infections, and in many cases these infections are not completely removed due to defective immune system function. These types infections have been consistently found in many ME patients, using more modern testing methods such as PCR tests and Taqman assays of blood, spinal floods and nerve, intestinal and muscle tissues and tissue biopsies from organs.

The inability of the dysfunctional immune system to rid itself of such pathogens keeps it in an activated state, yet ineffective state. In the 2-5a synthetase / RnaseL anti-viral pathway an unusual form of RNase-L has been found in ME patients - 37 kDa RNase-L. The ratio of 37 kDa to the normal 80 kDa form of Rnase-L is high in ME patients, and could be used as a diagnostic bio-marker. 37 kDa RNase-L can be six times as destructive as the 80 kDa Rnase-L. This fact is important as 37 kDa can be 1,500 times above normal levels in seriously ill ME patients. The 37 kDa RnaseL destroys human messenger RNA and disrupts protein synthesis throughout the body, and keeps the immune system abnormally activated. The interference with cell functioning caused by these highly elevated levels of abnormal RNase-L explains why ME patients are so sick. Disrupting protein synthesis in the cells, impairs the liver and the body's detoxification system and leads to a build up of toxins and free radicals. Also, increased (abnormal) immune activation increases the level of free radicals produced and oxidative stress in the body. Most studies reveal very high levels of oxidative stress in ME patients, which points to significant ongoing damage over time. The large increase in free radicals disrupts mitochondria and the Krebs cycle, causing great fatigue and continuing damage to the cells, internal organs and the body, which is cumulative over time. This impairs the body's ability to recover.

Research also suggests a link between STAT1-alpha deficiency in ME and protein misfolding and amyloid formation, meaning that ME has neuro-degenerative aspects similar to Huntingdons disease, Parkinson's disease, Alzheimer's disease, etc. The abnormalities in the 2-5a synthetase / RnaseL anti-viral pathway create fragments and research shows that they can interrupt cell metabolism and functions causing Chennelopthy. This in turn has multiple adverse effects on the body, such as ion channel disruption at cellular level, abnormal cell development, growth and death, potassium deficiency, low blood volume, vasoconstriction, frequent urination, irritable bowel, heart dysfunction, muscular abnormalities, breathing difficulties, hormonal imbalances, exercise intolerance, hyper-excitability, insomnia, etc.

The other immune system pathway - the PKR pathway is over activated and induces increased cell apoptosis (death) and increased inflammation through stimulation of NF-kB and COX2. These in turn stimulate inflammatory cytokines which produce significant pain and inflammation throughout the body. This explains much of the pain and inflammation seen in ME patients. They also stimulate Nitric Oxide and Peroxynitrite. Peroxynitrite causes cell damage, neuron damage, nervous system damage, reduces glutathione, damages mitochondria, blocks liver detoxification, adversely affects HPA axis, and can increase NMDA activity in the brain which can lead to sleep disruption and neuro-excitability. High levels of Peroxynitrite have been found in ME patients.

The viruses consistently found in ME share molecular homologies for autoimmune disease markers of the thyroid, lupus, MS. This may be leading to the autoimmune disorders found in ME, and to the effectiveness of Rituximab an autoimmune drug. This is fascinating as ME patients have many of the neurological symptoms found in autoimmune illnesses and MS.

HPA axis dysfunction causes severe disruption to hormones, particuarly the thyroid, the adrenals and the hypothalmus, and the immune system cells which depend on hormones, disrupts sleep and wake cycles, causes weight gain, causes intolerance to cold, sweating, poor circulation, acute intolerance to stress, tiredness and brain fog. The methylation cycle block and glutathione deficiency leads to choline-creatine imbalances in the brain, vitamin b-12 deficiency, deficiencies in hormones such as Melatonin, excessive homocysteine (a toxin), and increases in oxidative stress. It also interrupts the sulphur cycle and sulphur metabolism which in turn affects detoxification. This leads to a build up of toxins in the body. A recent research finding suggests that blocks in the methylation cycle and a deficiency of glutathione may lead to insufficent methylation and immune system function and to the re-activation of latent, endogeneous viruses in the human body. These latent, endogeneous viruses are inherited from parents and lie dormant in healthy people, but can be re-activated by certain factors. It is believed that insufficent methylation may be one of these factors. The immune system is dependent on methylation for it's functions and effectiveness, and defects in methylation has adverse effects on immune system function. This is the subject of continuing research by top scientific researchers. There is exercise intolerance, rapid lactic acidosis and long duration post-exertional malaise after exercise. Genetic studies also show dorsal root ganglia and sympathetic nervous system dysfunction, leading to impaired blood flow and metabolite removal (after exercise) from muscles and tissues, and accompanying high oxiative stress and glutathione depletion. Mitochondria and krebs cycle dysfunction causes an energy drain and reduces exercise capabilities and may lead to rapid lactic acidosis during exercise and to post exercise malaise lasting for days.

There is continuing damage over time, combinations of free radicals, toxins, heavy metals, viruses and pathogens cause damage to DNA, gene changes, damage to ion channels on the membranes of cells, damage to the brain, damage to the nervous system, damage to the heart. This in turn triggers further channelopathy, cognitive difficulties, nervous system dysfunction, heart abnormalities, damage to arteries including a stiffening of arteries, and further glandular problems. Risk of premature heart attack increases. The automonic nervous system is also disrupted, leading to orthostatic intolerance and Postural Tachycardia Syndrome (POTS). Analysis of gene abnormalities show disruption to serotonin processing, and this adversely affects sleep, digestion, pain and body fat. Other gene changes show disruption to norepinephrine, epinephrine, CRH and cortisol and this adversely affects blood flow, blood pressure, heart rate, digestion, stress response, the HPA axis and the glands. There is a domino effect with dysfunctions leading to other dysfunctions and abnormalities and so on over a period of time ; producting a patient with multiple dysfunctions. Ultimately, the immune system is re-set, the HPA axis is re-set, the nervous system and endocrine systems are re-set, the mitochondria and krebs cycle is re-set, the methylation cycle is re-set to provide a persistent illness, which creates domino effects of further biological abnormalities and dysfunctions over time.

Dr. Cheney who has over 20 years experience in treating ME patients and researching the illness has stated that ME progresses in 3 phases. The first phase involves the initial disruption to the immune system, mitochondria and krebs cycle and HPA axis and endocrine system. The second phase involves damage to more body systems including the liver, the brain, the glands, and the heart and worsening disability. The third phase involves multiple dysfunctions and abnormalities and a high level of disability. This is described in more detail in the Scientific Evidence Section.

The inherited genetic backgroud of a patient will also determine the path this illness takes, with subtle differences between ME patients ; thus there are several subgroups within the ME illness. Each individual has their own inherited genetic profile which makes him / her susceptible to certain illnesses - the trigger for these illnesses could be environmental toxins or pathogens or excessive free radicals or excessive stress or poor diet and lifestyle. Research now shows considerable interaction between the environment and one's genes, and resultant mutations and changes to gene expression, with accompanying changes to one's health. The ME patient becomes locked into a cycle of worsening illness over time, with pain, brain fog, insomnia, infections and total exhaustion being the most common symptoms. This then stabilises at a severe level of illness, making it very difficult or imposslbe to work or hold a job. Many patients become bed ridden or house bound or have to use wheelchairs.

Most of these scientific findings have been confirmed by genetic studies of the illness completed between 1999 and 2012, and from preliminary findings in ongoing genetic research. One study found 24 abnormally changed genes and another study found another 15 abnormally changed genes, another identified 88 abnormally changed genes, and another study found various alterations in 839 genes. These gene expressions correlate to the immune system, EBV infection and immune system reactions to this virus, the signalling system for the immune system, cell death, cell development and growth, protein synthesis, other viral infections and immune system reactions, re-activation of latent viruses, toxin exposure and toxin damage to the body, channelopathy at cellular level, neurological abnormalities, the brain, dorsal root ganglia and sympathetic nervous system dysfunctions, brain lesions, cortisol and HPA axis abnormalities, serotonin processing abnormalities, neuro-endocrine abnormalities, Krebs cycle and and mitochondria abnormalities found in ME . In addition, seven subgroups have been found in these genetic studies. The subgroups correlate to different degrees of severity of the illness arising from subtle differences in inherited genetic profiles between individuals, different exposures to environmental toxins, pathogens and potential mutation initiators, the initial status and strenght of one's immune system, different trigger mechanisms, different diet and lifestyles, and progression and duration of the illness. These genetic studies are outlined in the Scientific Evidence section on this web site.

However, larger genetic studies are underway in London, England under the supervision of Professor Paul Kellam, and will be completed in 2013. This research may identify more abnormal genes, initial causes of the illness, the domino effects and dynamics of the illness, more precise genetic diagnostic markers, and identification of medical drugs which may resolve some or many of the abnormalities and dysfunctions found in ME. Also, Dr. Henry Heng of Wayne State University is due to publish his findings regarding the link between genome instability and chronic fatigue syndrome in late 2013.

Though it is important to state that genetic research has yet to map all of the abnormalities and dysfunctions found in ME, and build a sytems approach linking abnormal genetic expressions and mutations to specific symptoms and dysfunctions in the body. And to establish a structure of causation from first cause to secondary effects and teritary effects and so on, and idientify the domino effects and interlinkage of body systems. This is explored in more detail in the Research Priorities section. We will be lobbying researchers and research foundations to do this. Furthermore, genetic medicines are not available and will not be available for a long time. The global economic depression which began in 2008 has halted, delayed and undermined a lot of medical and scientific research worldwide.

A Homogeneous or Heterogeneous Disease ?
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.

ME is according to scientific research a homogeneous illness with heterogeneous features. Whether this will remain a fact or not will be determined by scientific research findings in the future. It is possible that ME is several separate viral, myocplasma, bacteria, parasite, and toxin related illnesses which share some similarities. ME displays some heterogenuous features due to the following reasons ;

Illness Input Variables: the factors mentioned (i) to (xiii) above. Each patient may be adversely affected by 2, 3, 4 or more of these illness initiating factors. There would be very slight differences between each patient due to genetics and environmental exposures and diet and lifestyle. Whether a patient actually gets ME or B cell Lymphoma or other Cancer or no disease is determined by inherited genetic factors, environmental exposures, interactions of genes with the environment, different pathogen exposures, the initial strength and status of one's immune system, and susceptibility to viral induced immune system dysfunction, chronic stress, and the triggering mechanisms for the illness. Once ME is acquired these factors will determine the path it takes, and the subgroup one belongs to.

Illness Processing Variables:
(1) Immune system dysfunctions and deficiencies accompanied by viral / mycoplasma / pathogen infection (active and latent) and/or toxins. Defects in the 2-5a synthetase / RnaseL anti-viral pathway & PKR pathway with effects on immune system function and channelopathy which in turn has multiple domino effects on the body. And autoimmunity, with strong indications of B cell abnormalities. Increased vulnerability to opportunistic infections over time. Also some evidence of chronic inflammatory immune system from regular exposure to molds and mycotoxins.
(2) in most cases continuing viral, mycoplasma and other pathogen infections (both active and latent, including partially latent) of the nervous system, nerves, immune system cells, intestines, muscles, and other body organs.
(3) toxic build up in the body. Flow reversal in the liver and the brain. Chronic Cerbral Spinal Venous Insufficiency (CCSVI). Chronic Hepatic 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, immune system, nervous system, mitochondria and ATP production with serious effects for the patient over time. Cardiac dysfunction is believed to play a key role in the initiation of this flow reversal.
(4) dysfunctions of the central nervous system, the brain and the autonomic nervous system, and involves significant inflammation, lesions, autonomic dysfunctions and other abnormalities. This resulting from infections, inflammatory immune system, toxins, and mitochondria damage and dysfunctions. This adversely affects many other body functions
(5)
ATP, mitochondria & krebs cycle dysfunctions and abnormalities. Including abnormal mitochondria destruction and abnormal mitochondria membranes, structures and electron transport, which adversely affects the entire body. This may be due to chronic infections, toxins and oxidative stress. This is the most important factor as the mitochondria and krebs cycle produces ATP, and the immune system, the nervous system, the heart, the brain, the glands, and all the organs rely on the mitochondria and ATP. It also governs states of tiredness and exhausation. Cardiac dysfunctions in ME are also related to these mitochondria dysfunctions.
(6) methylation cycle blocks and glutathione deficiency throughout the body. Deficient glutathione increases oxidative stress and this contributes to mitochondria abnormalities and dysfunctions.
(7) 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.

Illness Output Paths: these are mentioned in the Research findings section above. They involve continuing damage to the immune system, mitochondria, liver, heart, brain, nervous system, HPA axis and endocrine system, blood vessels, cells, etc.. Dr. Cheney who has over 25 years experience in treating ME patients and researching the illness has stated that ME progresses in 3 phases. The first phase involves the initial disruption to the immune system, mitochondria and krebs cycle and HPA axis and endocrine system. The second phase involves damage to more body systems including the liver, the brain, central and autonomic nervous system, the glands, and the heart and other body systems and worsening disability. The third phase involves multiple dysfunctions and abnormalities and a high level of disability. This is described in more detail in the Scientific Evidence Section. The output being determined by

- 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

- the initial strength and status of one's detoxification system. Extent of flow reversal in the liver and brain and nervous system. Toxic build up over time.

- inherited genetic factors, including genetic weaknesses

- environmental exposures, including toxins and levels of oxidative stress in the body. And the interactions of genes with the environment, including toxins and oxidative stress factors

- different pathogen exposures over time

- 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. 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, 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.

.The seriousness of this physical illness over time has been outlined in the see Memorial section and the paper Patient deaths from ME. Output could be termed "cumulative damage over time."

ME is a complex, adaptive illness with emergence features over a period of time. It encompasses many of the findings in Complexity Theory and Complex Adaptive Theory and Emergence Theory as applied to biological systems. Scientific research will need to consider these features of the illness.

What has been done ?
Nothing has been done so far. There is no ME Clinic in Ireland and none in Northern Ireland, and no proper diagnostic protocols, no treatment protocols, no modern testing equipment, and no approved medicines for people with ME in Ireland today. ME patients are being left to suffer and in many cases die from their illness. This situation is unacceptable

ME research has been under-funded or not funded in many cases for 30 years in Ireland, the UK, Europe and the North America and Asia. Many research projects into the biological causes and biological dysfunctions in ME have been rejected over the years by government research bodies. Yet, ME has imposed and continues to impose large losses on economies - in the USA it is estimated to cost $100 billion per year, in Ireland 2.54 billion euros per year, in Britain £30 billion per year (See 'Why set up a clinic ?' section on this web site). These are huge losses, yet ME receives far less funding than other similar ilnesses. The following passage from the Health Rising web site, explains the situation very well:

"And per person afflicted? According to the Fair Allocations In Research Foundation in 2013 cancer research received $4,400 in funding per cancer patient. Compare that to the $150 per patient prostate cancer and Parkinson’s Disease research receives yearly. Then compare that to the $85 per patient for Alzheimer’s research and the $45 per patient for Hepatitis B.

Finally compare that to the funding for ME research: $6 per patient per year!

Based on prevalence, suffering and societal costs, the funding for ME in the US is about 20-30 times smaller than it should be. For instance, multiple sclerosis (MS) prevalence is about half that of chronic fatigue syndrome yet multiple sclerosis’ NIH  budget ($120 million) is 20 times higher than that of ME . Both ME and asthma cost the US economy around $20 billion per year in economic losses, yet asthma gets 40 times as much NIH funding ($250 million/year)."

By calling ME an imaginary illness psychiatrists have undermined the credibility of ME and this has affected it's research funding from governments. One research institute in the USA embezzled funds which were designated for ME research in the 1990's based on the false psychiatric premise that it was an imaginary illness. While the Medical Research Council (MRC) in Britain was found to have had psychiatric bias in it's funding for ME research for over 15 years according to the findings of the Gibson Report (UK House of Parliament). In the case of the denial of research funding by governments and national health institutes and research institutes worldwide, it is estimated that certain psychiatrists have been responsible for denying $600 million in research funding into ME over 20 years. This $600 million could have made a huge difference to scientific research and brought the world much closer to understanding the structure of causation of the illness and it's biological dynamics and led to the development of medical drugs to treat the illness.

It's time for action, many ME patients, carers and relatives have been lying around waiting for "miracle cures" for several years and decades, throwing money here and there, and they have been disappointed and will continue to be disappointed because they have been looking in the wrong direction. It's time for them to change their outlook and direction ; thousands of ME patients have recovered through very specialised and thorough medical support, and this web-site and campaign aims to enlighten patients, carers and others of this fact. We also aim to put the relevant facilities, technologies and medical drugs in place to facilitate full recoveries from ME in Ireland and elsewhere.

Many of the medical abnormalities found in ME cannot be detected in standard medical tests in Ireland. New diagnostic methods, new criteria, and high-tech blood tests are required to identify the specific medical abnormalities found in ME patients ; these tests are currently not available in Ireland. A special Clinic would have the resources to invest in this technology and could serve as a focus point for diagnosing and treating the illness in Ireland.

However the work of dedicated scientists, researchers and doctors from around the world since 2003 has provided new hope for ME patients. It is now possible to get a diagnosis of ME which is highly accurate and focuses on a number of serious biological abnormalities, dysfunctions and infections. This is outlined in our clinic proposal.

ME Clinics and Medical Drugs & Treatments and Recoveries from ME
At present, the Irish Medicines Board and Irish Medical Council have no approved medicines for treating ME patients. Doctors often prescribe pain killers, tranquilizers and sleeping tablets for ME patients but these medicines are not approved by the Irish Medicines Board and doctors may be breaking legal and ethical guidelines in prescribing these medicines. The important point here is that no medical drugs have been approved by the Medical Authorities for treating ME. This is appalling considering the fact that many developed Western countries have approved medicines for treating ME, and in a number of cases there have been total recoveries from ME, most notably from the drug Ampligen.

Certain new drugs have been found to be very effective in the treatment of ME in the USA, Canada, Mexico and Belgium. Most Irish doctors, the Irish Medical Council and the Irish Medicines Board have never heard about these new ME drugs as their knowledge of such matters is several years out of date. This lack of knowledge means ME patients are being deprived of treatments which could greatly improve their condition and bring about recovery in a majority of cases. To worsen this situation, certain so called "ME experts" claim that there is no cure for ME. These claims are false and bogus. 

Doctors in the United States have had success in treating thousands of ME patients, and there are medical reports and research to back this up. In other words thousands of ME patients have recovered through proper and thorough medical support. The following clinics have successfully treated thousands of ME patients bringing about full recovery in the majority of cases:

North America and South America

  • The Cheney Clinic in the USA . Dr. Paul Cheney has been treating ME and CFS since 1985. He was one of the doctors involved in treating patients in the Lake Tahoe outbreak in the mid 1980's in the USA. He is a highly regarded medical doctor and researcher, and is one of the most knowledgable doctors on ME and CFS in the world.
  • Dr. Daniel Peterson, is a well known ME and CFS doctor and researcher. He has been treating the illness since 1985, including treating victims of the Lake Tahoe outbreak in the 1980's. He has a very comprehensive knowledge of the illness. He currently works in Sierra Internal Medicine Associates 926 Incline Way, Incline Village NV 89452. Tel: (775) 832-0989
  • Dr. Byron Hyde has been involved in ME treatment and research since the mid 1980's and is one of the most experienced ME / CFS doctors in the world. Address: Dr. Byron Hyde, Nightingale Research Foundation, 121 Iona Street, Ottawa, Ontario, Canada. Book an Interview with Dr Byron Hyde on Skype or iChat Video
  • Dr. Lucinda Bateman's medical clinic in Utah, USA. Dr. Bateman is a highly respected and well experienced medical doctor who has been treating ME / CFS patients since the late 1990's. 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 bodies.
  • Dr. Alison Bested, in Toronto, Ontario. She is a highly experienced doctor who has been treating ME and CFS since the late 1990's. She was one of the authors of the Canadian criteria (2003).

Europe

  • Dr. Sarah Myhill's Clinic in Britain. Dr. Sarah Myhill is a distinguished and highly regarded medical doctor and researcher based in Wales. Dr. Myhill has been treating ME patients and researching the illness since the mid 1990's.

Australasia, Asia and Africa

  • Dr Hugh Derham
    Bicton - Healthquest - Point Walter Medical Centre
    322-324 Canning Highway (Cnr Point Walter Rd) Bicton WA 6157. Phone: 08 9438 2299
    Bicton - Bicton Medical Centre
  • Ehlers-Danlos Syndrome (EDS), commonly found in ME and CFS patients
    - The Royal Melbourne hospital familial cancer Centre, affiliated with Melbourne University has a genetics section dedicated to connective tissue diseases including EDS.
    - Royal Childrens Hospital - Professor Ravi Savirayan and Mr Gary Nattrass - recommendation from EDS Australia group
    - Monash Children's Hospital - Professor Sue Piper - recommendation from EDS Australia group
  • POTS commonly found in ME and CFS patients.
    - The clinical pharmacology department at the Austin Hospital which is affiliated with Melbourne University includes Specialist POTS Diagnosis and treatment.
  • Dr. Rosamund Vallings, New Zealand. A medical doctor with over 15 years experience treating ME/CFS patients and researching the illness, and one of the authors of the Canadian Criteria (2003) and International Consensus Criteria (2011)

Thousands of ME patients have recovered as a result of the treatments received at these Clinics and doctor's practises mentioned above. These ME patients decided to take responsibility for their own health and pursue a course of treatment which would enable them to recover from ME.

ME research has been chronically under-funded and in many cases not funded for the last 40 years. This lack of research funding and projects led to stagation, and inadequate understandings of the illness. While there has been some money devoted to biological and biomedical research which has helped us understand the disease better, significant amounts of research money was wasted on psychiatric research which has proved useless. The appalling state of ME research means that a "miracle cure" or "miracle drug" which will magically cure all cases of ME is at least 20 years away or possibly even longer ; most patients cannot wait this long and why should they have to wait when there are treatments available today which can bring about recovery from ME. It is highly unlikely that one medical drug will miraculously cure ME.

The ME clinics which have successfully treated ME patients and brought about recoveries show that it is possible to deconstruct the abnormalities and dysfunctions present in ME via intensive medical tests, biomarkers and objective biological data, and treat these with medical drugs and clinical nutrition and healthier lifestyles.

Next page
Overcoming Prejudice, Discrimination, Stigma and Lies

 

 


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