- Last Updated: 05 December 2015 05 December 2015
by Dr. Ros Vallings
IiMEC8—Infection, Immunity and ME—Mainstreaming ME Research
31 May 2013, Westminster, London
I was privileged to attend the 8th IiME conference in London on 31st May 2013. This conference was preceded by a one day symposium gathering together 34 clinicians and researchers from a number of countries. The presentations, brainstorming and discussion will, I am sure, lead to much collaborative research, sharing of ideas and furtherance of understanding of this complex and very serious illness.
History of ME/CFS and the FDA Stakeholders meeting
The conference itself was well attended by delegates from 11 countries, and was opened by Dr Ian Gibson. The conference began with an address by the keynote speaker, Dr Dan Peterson from Nevada, USA. He initially outlined some of the history of ME/CFS and reflected on the past. He explained that criteria for diagnosis were established 25 years ago, and emphasised the fact that a single set of criteria needs to be used internationally. He talked of the history of the illness from 1980 up to the present time. In the UK the prevalence has been estimated as up to 1-2% of the population. There is similarity in the symptoms, levels of severity and course of the illness worldwide. It is costly to treat: 9 billion US dollars in direct costs and 51 billion in indirect costs in the USA. The current accepted model of the illness is genetic vulnerability, an event such as infection, trauma, stress etc and mediators finally leading to a diagnosis of ME. He described 4 steps in management of illness generally: 1) a specific diagnosis, 2) assessment of severity and prognosis, 3) therapy and 4) assessment of effectiveness. This model does not fit ME. There is no biological marker, no definite drug and no endpoint.
He went on to describe the recent FDA stakeholders’ meeting in the USA. Points discussed included the general nature and extent of the disability, lack of treatment and acknowledgement of much research accomplished. The take-home messages were the fact that one does not necessarily need a biomarker, it takes 8-15 years for drug development, a drug can be approved or withdrawn, a drug can be re-purposed, and validated endpoints are needed. Potential solutions can involve computational analysis (genetic, not just biological), work with novel pathogens (samples needed from various tissues), immunological biomarkers (defining subsets), end point evaluation (e.g. approval of ampligen has been denied, but VO2 max approved as a suitable test for ME), drug development (e.g. rituximab needs large trials in multisites). In summary he expressed the importance of the need for worldwide collaboration, definition of the mechanism of the disease and establishment of centres of excellence.
IT, social information, and bio tech revolutions influence medicine
Dr Andreas Kogelnik, (Stanford, USA) founding director of the Open Medicine Institute spoke of the changing world involving the IT revolution, the social information revolution and the biotechnology revolution. This has all changed the way we look at medicine. He describes this as a health/disease revolution. He provided some graphs of how things have changed. e.g., the number of processors on a chip has doubled every 18 months since 1981, while the cost per megabyte is decreasing from $700 per megabyte in 1981, to less than 2c per megabyte now. There are 2 cell phones for every individual in the USA. There are now many wearable devices for evaluation of physiology. In POTS patients this can include continuous measurements, so that it is easy to document activity etc. efficiently and accurately.
Social networking has also had an impact on medicine—e.g., there are 1 billion facebook users worldwide, so that people can get medical information this way. Biotechnology has increased explosively in relation to storage. The cost of mapping the human genome is decreasing rapidly and now one can pull out a huge amount of data for $20,000. It is becoming possible to cluster and regroup patients by moving into a molecular level. There are 5 stages for acceptance of a new idea: 1) Irrelevance, 2) Relevant but unproven, 3) Proven but dangerous, 4) Safe but not saleable and 5) It will sell —great idea! ME has largely been ignored as there has not been enough data. The current state of the science is that there are a lot of hypotheses, there is a start on data, there are willing people to collaborate, we have measurements that have not yet been applied to ME and there are patients willing to help. Measurements need to be broad and deep and there must be large numbers of people engaging.
Kogelnik then went on to describe the MERIT initiative. they had a roundtable discussion in New York in June 2012 with 25 clinicians and researchers gathered. The result was a list of priority targets for collaborative research, which could lead to open collaboration and a worldwide plan. As a result 10 research projects are being established.
1. Large scale combination trial of rituximab and valganciclovir
2. International registry and biobank
3. Protein panel in treated and untreated patients
4. Phase 2 treatment of mono and combination pharmacological pilots
5. Immunological biomarkers – exploration studies (NK cells, B and T cells)
6. DNA studies: whole genomes, HLA sequencing, DNA methylation.
7. Mass spectroscopy – environmental measures
8. Comprehensive viral testing
9. Advanced immunological biomarkers
10. Non-pharmacological studies, which need standardisation. One arm is looking at the evaluation of how Moringa affects NK cells. Included also are projects looking at insurance issues and also possible related diseases (Lyme, autism).
Patients can now register on line to be included in the databases for future possible research [www.openmednet.org/registration/MECFS].
Gulf War Illness
Rakib Rayhan (Georgetown, USA) gave an overview of Gulf War Illness (GWI), which is closely related to ME/CFS. The first Gulf War was in 1990-91. There followed an excess prevalence of veterans with generalised symptoms and also recognised medical conditions. By 1991 there were many with ongoing illnesses with no firm explanation and these people were initially labelled as psychosomatic or malingerers.
However it was established eventually that oil fires, smoke, incomplete combustion and fire particulate materials maybe responsible. A task force was established in 1997 to look into GWI. Sarin (an anti-cholinesterase inhibitor) and pyridostigmine use was investigated. Many other possible causes of a complex nature were investigated, such as involvement of pesticides and other chemicals.
Objective measures on patients included exercise induced effects on cognitive function using functional MRI (fMRI) on 2 consecutive days. Diffusion tensor imaging and voxel-based technology was used. The data presented is the first direct evidence that 1) there is white matter damage associated with the complaints of pain and fatigue, 2) there was elucidation of two phenotypes in response to exercise stressors, 3) neurological evidence of compensatory cognitive function, 4) cortical, cerebellar and brainstem damage associated with exercise induced phenotypes, and 5) cognitive alterations associated with abnormal energetics of lactate metabolism in the prefrontal cortex, possibly linked to neuronal mitochondrial dysfunction. The orthostatic heart rate was elevated in some patients and in these, tenderness in FM points increased after exercise. There were changes in brain blood flow particularly after exercise. The conclusion was that chemical exposure may have damaged the CNS, and the study emphasised the importance of measures such as fMRI being taken before and after exercise.
Retroviruses and ME
Professor Greg Towers (London, UK) has studied the lifecycle of retroviruses and spoke on the relationship between retroviruses and ME. He went through the reasons as to how and why XMRV is not a human pathogen, but a mouse gamma retrovirus. He outlined the initial prostate study which had described XMRV as being present in prostate cancer. He outlined the basic steps of retroviral replication, and explained how endogenous retroviruses get into the genome. He showed how cells will grow if injected into mice but not in a laboratory dish. Excitement originally arose because if XMRV had been implicated in ME, it could lead to potential diagnosis and treatment. After the original XMRV discovery by the Mikovits lab, there were a series of negative studies, and the subsequent conclusion that XMRV was a laboratory contaminant. Towers had looked to see where the ancestral strains had arisen. The cell line had come from mice, and was then intermingled with the human line. They were not separate sources.
The Lipkin study provided the final closure using 150 patient samples and 150 controls, analysed blinded in different centres. There were no differences between samples and controls, and it was finally concluded that XMRV is not a human pathogen. It is a mouse virus generated around 1994 and not aetiologic of ME. Genetic evidence can be used to determine origin. It was also concluded that PCR is very sensitive and needs to manage inevitable contamination.
Towers emphasised that “This should not ever happen again” and new pathogens need more rigour.
Pathogen discovery in ME
The next presentation was from Professor Mady Hornig (New York, USA). Her focus was on pathogen discovery in ME, in particular in relation to pathogens implicated in brain disorders. She looked at the role of microbial, immune and toxic stimuli in the development of neuropsychiatric conditions including, autism, PANDAS (paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections), mood disorders and ME. She described a 3-strike hypothesis involving genetics, environment and effects on the foetus. She used the risk of schizophrenia after cannabis exposure as an example. The exposure alone does not lead to the disease—there needs to be genetic susceptibility. In ME, it is unlikely there is a single agent. Many other disorders have an immune generated pathogenesis. In 1957, the autoimmune concept associated with disease was proposed by Witebsky.
In ME, early evidence associated with onset may not be available. There may be direct evidence of effects at infection sites. Replication may cause cell damage, toxins may alter physiology an there may be effects distal to the infection site. Host responses may influence outcomes. Interference with differentiated cell function and molecular mimicry may occur, and there may be long term effects of infection.
Infection may be “hit and run." In MS there are for example geographic regional effects also. Microbes can condition the immune system via the gastrointestinal tract. Gut microbiota can modulate brain and behaviour, leading for example to effects on sleep and alertness. CNS function depends on a balance between the immune system and stress responses. There is memory dysfunction if the pathways are not operative.
Other studies by Hornig have shown no association between measles virus and autism or bronavirus in schizophrenia. She has however found reduced ileal enzymes, which may lead to failed uptakes of precursors of anti-oxidants. This can lead to oxidative stress. She has several ongoing ME studies relating to this, including looking at the timing of flu and enteroviral infections. She had a brief look back at some of medical history—at how duodenal ulcers were originally thought to be stress related, and were later shown to be due to H.pylori infection. And quotes from Einstein relating to exam questions—when a student asked why the questions to the current year’s exams were the same as last year, he was told, “but the answers will be different this year “– showing us that medical science is constantly in a state of change.
NHS and ME in the UK
Dr Clare Gerada is now the chair of the Royal College of Physicians (UK)—and she spoke about the government NHS reforms and implications for long term conditions such as ME. The RCGP is the voice of 48,000 GPs in the UK, and has just celebrated its 50th birthday. The aim of the reforms is to build bridges and improve the lives of patients, particularly those suffering from chronic disability. She described general practice as the oldest branch of medicine, and as a GP herself, she has seen many changes in general practice and in the NHS over the past 3 years. The aim of the GP (as quoted by her own GP father) should be to give something back to the community, listen, and be there for patients. One million patients are seen in Britain daily by GPs.
General practice is under great strain. There is lack of money and manpower, and it is hard to deliver the standard of care needed from cradle to grave. The whole health service is under pressure too because of the ageing population and increasing demands on services. There are more complex problems with age and this can be time consuming. What matters most is continuity of care. The patient also needs to learn to help manage their own condition. There is a need for development of integrated services.
Ideally the GP needs access to a multidisciplinary team. The NHS has had a huge reorganisation, and all existing structures were dismantled. There has been rebuilding with monumental cuts, which has led to exhaustion and demoralisation. GPs have now been relegated to local groups, and healthcare is then bought for these populations. There are many social changes, and public health is being run by local governments.In relation to ME, very few GPs fully understand the illness, as there are so many illnesses and so much detail to learn all the time. It is an illness that needs specialist care, as is far too complex and time consuming for the average GP. However the RCGP is trying to improve things by providing online education. 500 GPs have downloaded the latest training module which should give greater understanding. The new NHS act will hopefully gradually improve things in the UK. Bridge building between the GP and patient is needed, and acknowledgement of the illness is slowly improving.
Immunological abnormalities in ME
Dr. Don Staines (Gold coast, Australia) then presented an update on the work by Sonya Marshall-Grasilnik, who was unable to attend the meeting. He outlined the new research being undertaken at Griffith University, where there is a dedicated ME research facility, which includes a 3 bed unit for 24 hour stay. He stressed the importance of getting immunological and molecular markers for this multi-system disease. He outlined natural killer cell (NK) function showing the release of lytic proteins: perforins and granzymes (A and B).
Studies show that NK-cell function declines over time in ME. CD107a is a NK marker for lysis, and granzyme B is down in ME.
Several dimensions show impaired function in the immune system in this illness such as: CD56 (bright) down, CD8 lysis down++, reduced respiratory burst in neutrophils and high levels of HNA2. There are also a number of significant differences in microRNA in ME. mRNA CD8 cells show consistent abnormalities.
He asked the question—is ME an autoimmune disease? Other abnormal results from their lab included upregulation of T-reg cells in the adaptive immune system—this could be a potential biomarker, and helps to suppress inflammatory mechanisms. No differences were found in gamma-delta cells, but this will be redone.
B-cell phenotypes showed reduced immature cells, despite increased memory and increased plasma levels. Plasmacytoid dendritic cells were elevated. Conceptual paradigms were outlined in the innate and adaptive immune systems, whose components are initiated in response to an adaptive pathogen.
Results indicate potential hallmarks of autoimmunity. There are clear derangements in the immune system, and he reiterated the fact that such major changes will never be fixed by “exercise”!
It is important to note that severe patients were included in these studies by going into patients’ homes to take the blood.
Clinical immunology and research on B-cell abnormalities in ME was discussed by Dr Amolak Bansal (Surrey, UK). He talked about immune dysfunction and autoimmunity. He looked at a long list of potential causes of ME, with interaction of the various systems, and a list of predisposing factors. He showed that 10-15% patient do have joint hypermobility. There is a slight familial tendency and relationships to personality and race. Fibromyalgia, IBS and MCS all can co-exist.
There is often a past history of mood disorders. Triggers can include infection, stress, vaccinations, injury, major life events etc. Factors which adversely affect the illness include sleep abnormality, over-activity, infections, anxiety and depression, inactivity, iatrogenic illness, illness beliefs, pessimism and loss of confidence.
He said that persistent stress can have an adverse effect on the immune system, stimulates the hypothalamo-pituitary axis and increases cortisol levels. Stress raises the predisposition for autoimmunity, upregulates the Th2 mechanism and downregulates TH-1 and T-regs.
Many symptoms occur associated with viruses and ME, but there is no evidence of overt antibody, complement or neutrophil change. There is NK-cell immunodeficiency. There have been very few useful studies looking at the immune abnormalities in ME.
There are no abnormalities on routine tests. Occasionally increased atypical lymphocytes are seen. CRP is usually normal. Altered NK function is not always found.
There are many inconsistencies. This may be due to use of different criteria, varying severity of illness, roles of exercise, sleep and stress, different methods and technologies used and the timing of tests.
Bansal asked several questions: What is the role of exaggerated receptor solubilisation, and cytokine/cytokine receptor autoimmunity in this illness? Are patients generating antibodies? He had looked at many immune parameters for antibodies and all were negative. However, transitional B-cells were elevated in ME patients, plasmablasts reduced and naïve B-cells increased. Some cytokines were abnormal and there were some T-cell subset abnormalities.
His conclusions were:
1) B-cells not being regulated properly
2) No evidence of autoimmunity to presently recognised organ specific and neuronal antigens
3) Reduced antiviral cytokines
4) Impaired T lymphocytes
5) Increased T viral effector cell numbers.
There is possible B-cell dysregulation initiated by a virus, the B-cells may produce autoantibodies, which can contribute to arousal mechanisms. They may target the mitochondrial proteins, leading to post-exertional malaise. Removing the autoantibodies reduces symptoms, but there is need to suppress the activity of the viruses, which encourage survival of autoreactive B-cells. Antivirals such as acyclovir and valcyte may be useful. He summarised by reiterating that this is a very complex disease.
Immunological basis of ME
The immunological basis of ME was addressed by Professor Carmen Scheibenbogen (Berlin, Germany). She explained how we are looking for the missing pieces of the jigsaw. There is evidence for immune mediated disease in the clinical picture, the laboratory finding and the efficacy of immunological treatment with drugs such as rituximab, ampligen, immunoglobulins and interferon alpha. There are controversial phenotypes immunologically in ME. Elevated T-regs and low NK toxicity are reproducible.
There is some immune activation and some immunodeficiency. She discussed cytokine analysis undertaken by Luminex. In further studies, 50% of patients were found to have elevated T-cell function with a TH-1 to TH-2 shift. Phenotyping was done by flow cytometry and there was T-cell activation in 2/3 of the patients. There was lymphopenia in a subset of the patients.
Polyclonal immunoglobulin was elevated in 25% of patients and there was evidence for immunodeficiency in a further 25%. There was MBL deficiency in 15% (and 7% in controls)—making these patients more prone to infection. There was evidence for ongoing infections with herpes viruses. A subset of patients (those with onset associated with EBV and those with recurrent herpes lesions) who improved on valaciclovir. She recommends trying a course in these patients. Some patients may have ongoing EBV activation. The data is controversial as there may be enhanced or diminished EBV responses. The team had done EBV sero-array and measured antibody response against more than 2000 peptides from EBV. There was significant difference between patients and controls.
The conclusion was that there are some distinct entities corresponding to different types of the illness. There is evidence for activation, deficiency and non-immune ME.
B-cell lymphocyte depletion in ME has previously been reported by Dr Oystein Fluge and Professor Olav Mella (Bergen, Norway) and as yet there is an embargo on disseminating their further research as it is awaiting publication. A further report on their findings will be added following journal publication.
They described again the studies undertaken up until 2011, when initially 3 lymphoma patients with ME had responded to the B-cell depleting drug rituximab. 2 infusions had been given 2 weeks apart (500mg/m2). A further study was then undertaken with 30 subjects (15 patients and 15 controls). 67% of patients had positive results and only 13% of controls. No major toxicity or adverse events were described. Duration of response was 8-44 weeks, with 2 patients having no relapse to date. In the majority of patients relapse occurred over time.
Further studies to be reported in the literature very soon include 26 patients being followed over 28 months using rituximab with a different drug regimen, and a further 8 very severely ill patients.
Towards the end of the proceedings, Ellen Piro (Oslo, Norway) presented Invest in ME with a special award acknowledging all the effort in organising these conferences, bringing together so many distinguished researchers and clinicians from around the world, encouraging collaborative research and enabling patient participation.
An award was also given to Professor Malcolm Hooper for his great efforts over the years. I would like to add my thanks to all these people, and in particular to both Invest in ME and the Alison Hunter Memorial Foundation. I must also thank ANZMES for giving me the opportunity to attend such a wonderful event.
Rosamund Vallings MNZM, MB BS
Conference DVD available for order - click here http://www.investinme.org/IiME%20Conference%202013/IiMEC8%202013%20DVD%20Order.htm
Permission granted to post. Original conference report by Dr. Vallings can viewed at: http://www.investinme.org/IiME%20Conference%202013/IIMEC8%20Conference%20Report.htm
- Last Updated: 03 January 2016 03 January 2016
An advisory panel set up by the Food and Drug Administration (FDA) voted on Friday, January 25, 2013 for tighter restrictions to be placed on Vicodin and other hydrocodone products.
Vicodin/ hydrocodone products are currently classified by the U.S. Department of Justice Drug Enforcement Agency (DEA) as Schedule III Controlled Substances, a category of drugs considered to have a lesser potential for abuse than those in Schedule I and II.
Physicians can prescribe medications from the Schedule III category using one of several acceptable methods: written, oral (by phone), or by fax and this medication can be refilled 5 times within a 6 month period.
In contrast, prescriptions for Schedule II medications must be written out, one for each month, and with no refills. Physicians must follow additional rules, limits and reporting regulations as well as the pharmacies that dispense controlled drugs (in how these drugs are stored, record keeping, and notification protocols).
The DEA claims Vicodin/hydrocodone products are now the most frequently abused painkillers in the U.S., caused by fairly lax prescribing practices of Schedule III drugs. This agency asked the FDA to convene a panel to review and make recommendations about the reclassification of these specific pain medications. The majority of the panel viewed Vicodin/hydrocodone as being pharmacologically comparable to opioids and having similar potential for abuse, therefore, they recommended reclassification of these pain medications as Schedule II controlled substances (along with opioids).
Conflict of opinion surrounds this recommendation for tighter prescribing restrictions. Some members of the medical community, pain medicine societies, and advocates believe this change will cause undue hardship for patients.
Addiction specialists feel the extensive use and accessibility of these particular painkillers increases the risk of overdose, addiction and/or abuse, including by people who use them for non-medical reasons and who may steal them or obtain them illegally from drug dealers.
While the FDA has not yet made a decision as to whether it will adopt these recommendations, it is important to realize this is not a new development.
The debate and push (by way of public petitions) to have hydrocodone /hydrocodone-combination products be placed under the more restrictive category of Schedule II substances has been going on since 1999. A few months earlier, a leading national newspaper ran a story about tactics used by the DEA to crack down on the growing problem of painkiller use/abuse such as arresting doctors who were overprescribing these drugs and closing down pharmacies that dispensed too many painkillers or were charged with other violations.
Wholesalers have also been targeted (i.e., referred to as the “middlemen” between pharmaceutical companies and pharmacies) for sending large shipments of controlled substances to certain pharmacies or locations or being charged with failure to report suspicious shipments to the DEA—some distributors have lost their licenses as a result and others have restricted or terminated shipments to pharmacies that could pose a threat to them.
This problem appears to be worse in some states (like Florida, known for its “pill mills”) forcing patients to travel extensively in search of a pharmacy that would fill their prescription. While prescription drug abuse has increased substantially over the past 10 to 15 years, access to pain medication/ pain management needs to be protected for people who legitimately suffer from chronic pain.
The White House, Office of the National Drug Control Policy issued a Press Release on October 1, 2012 which describes a new program they will offer, White House Drug Policy Office and National Institute on Drug Abuse Unveil New Training Materials to Combat National Prescription Drug Abuse Epidemic. This program is created for physicians, medical interns and residents so they can learn how to properly prescribe pain medications and address prescription drug abuse. This initiative is sponsored by the National Institute on Drug Abuse (NIDA) which also allows participating healthcare professionals to earn continuing medical education (CME) credits.
For more information
“FDA Panel Votes for Tighter Controls on Vicodin” by Kristina Fiore (MedPage Today) published on January 25, 2013, available at: http://www.medpagetoday.com/PublicHealthPolicy/HealthPolicy/37024
“F.D.A. Panel Votes to Restrict Drugs Like Vicodin” by Sabrina Tavernise (New York Times) published on January 25, 2013, available at: http://www.nytimes.com/2013/01/26/health/fda-vote-on-restricting-hydrocodone-products-vicodin.html
“A New Painkiller Crackdown Targets Drug Distributors,” by Barry Meier (New York Times ) published on October 17, 2012 available at: http://www.nytimes.com/2012/10/18/business/to-fight-prescription-painkiller-abuse-dea-targets-distributors.html
“White House Drug Policy Office and National Institute on Drug Abuse Unveil New Training Materials to Combat National Prescription Drug Abuse Epidemic,”— Press Release issued on October 1, 2012, that can be viewed at: http://www.whitehouse.gov/ondcp/news-releases-remarks/ondcp-nida-announce-new-elearning-tools-combat-rx-drug-abuse
- Last Updated: 19 November 2015 19 November 2015
“Why Doctors Can’t Diagnose and What Tests Should be Considered” was the title of the lecture by Dr. Byron Hyde, Founder and Director of the Nightingale Research Foundation, Ottawa, Canada, co-sponsored by the Massachusetts CFIDS/ME & FM Association and the Massachusetts Department of Public Health on Saturday, October 27, 2012.
Dr. Hyde's Background
Several incidents early in Dr. Hyde’s life shaped his capacity for empathy. In the eighth grade, he developed polio, which he felt gave him an advantage compared to other doctors. He was unable to go to school, and while at home he became a prolific reader. After a year he was able to return to school but he learned first-hand what it was to be disabled.
He also has suffered with migraines since he was a young teen. While studying at the University of Toronto, during one of his last exams in history, a subject in which he was getting excellent grades, he was unable to take the final because of a migraine. The physician did not believe him; and this doctor’s response led Dr. Hyde to affirm he would always believe his patients when he, himself, became a doctor.
Dr. Hyde explained that physicians do good work and make excellent diagnoses in about 90% of their patients. However, in the remaining 10%, which would include Chronic Fatigue Syndrome (CFS), Myalgic Encephalomyelitis (ME) and Fibromyalgia (FM) patients, physicians do not have enough understanding or time to make a complicated diagnosis, and instead make what Dr. Hyde called the “Educated Guess Diagnosis”. He suggested that doctors rarely look for multiple causes of illness. Dr. Hyde, in fact, has rarely found just one cause in a complicated illness.
Dr. Hyde divided his lecture into a section on ME/CFS and then Fibromyalgia, though some topics were addressed simultaneously.
What piqued Dr. Hyde’s interest in ME?
In August 1984, after an epidemic outbreak in Canada, Dr. Hyde traveled to the Centers for Disease Control and Prevention (CDC) in Georgia, with the intention of learning what he could. The CDC knew nothing of Myalgic Encephalomyelitis (ME) but referred him to a Dr. Charles Poser (1923-2010) from Harvard University, Cambridge, MA.
Dr. Poser was one of the world’s leading physicians in Multiple Sclerosis (MS). It was Dr. Poser who piqued Dr. Hyde’s interest in learning about ME. Dr. Poser had developed the criteria for Multiple Sclerosis, proving that MS was due to Central Nervous System (CNS) neuron injury.
Many patients were referred to Dr. Poser for a traditional MS work-up. In doing the early Magnetic Resonance Imaging (MRI) on ME patients, Dr. Poser did not see brain lesions commonly found in MS, but what he did find in common with both illnesses was oligoclonal banding.
Dr. Hyde stated that if sudden onset patients had both a blood test and cerebrospinal fluid checked at the same time for this oligoclonal banding, and the banding is positive, then they either had MS or ME. What is important about this finding is that oligoclonal banding occurs when there is neuron breakdown—nerve cells in the brain being injured on an ongoing, chronic basis.
Dr. Poser sent Dr. Hyde to England to study ME with Dr. John Richardson, a country GP from Newcastle, UK. There, Dr. Hyde ended up staying a month and absorbed all he could. Dr. Richardson had ME himself, and followed over 4 generations of patients demonstrating genetic and physical factors governing the illness of ME patients. Dr. Richardson worked until the time of his death at age 80. Upon Dr. Hyde’s return to Canada, Dr. Poser started sending ME patients to Dr. Hyde.
Acute onset of ME/CFS caused by brain injury
Having been trained as a forensic physician, Dr. Hyde put his curiosity to work asking the questions “why?” and “what is behind ME?” He believes that the acute onset of ME/CFS is caused by an injury to the brain and it can be seen as a diffuse encephalopathy.
Unfortunately, Dr. Hyde thinks most neurologists miss this diagnosis because it does not show up with traditional neurological testing. He said that is due to the fact that the symptoms reside in the vascular system.
Diffuse encephalopathy, however, does show up on SPECT, PET (with the proper software) and BEAM scans (electronic computer-driven EEG), but a physician has to have enough knowledge of the tests to order them.
From a forensic point of view, Dr. Hyde suggested another simple test: carotid and transcranial doppler. This test looks at blood flow through the main arteries going into the brain and was developed at Haborview Hospital in Seattle, WA.
If all these tests show a blood diffusion problem in the brain, physicians and insurance companies cannot argue that there isn’t a problem. This is called forensic triangulation (based on an engineering principle).
A stroke patient can exhibit similar symptoms to the ME/CFS patient in the area of aphasia (word finding difficulty and speech difficulty) and dysphasia. Dr. Hyde does not see much difference between stroke and ME/CFS patients with regard to diffuse brain injury.
Why doctors can't diagnose
Dr. Hyde agrees that doctors are brilliantly trained, but they aren’t compensated for their time to do an in-depth evaluation of patients. He pointed out that years ago, physicians were wealthy and that is no longer the common case. Now, they are burdened with too heavy a patient load and not enough time. Without an appropriate reimbursement schedule and extra help doctors either can’t or won’t spend the time.
Dr. Hyde gave an example of how he writes up an order for an MRI; he uses up to a two-page summary listing all the details of the patient’s symptoms and what he is looking for. Radiologists are so intrigued they want his patients.
Many times physicians are not able to do what would seem logical: ordering and obtaining tests; examining results; reading consultation reports; going to the hospital to review complex tests, or question the consultant or hospital specialists on test results.
In a further explanation, Dr. Hyde used the Mayo Clinic in Rochester, MN as an example saying “They do a very good and expensive job with many illnesses, but CFIDS/ ME is not among them. Having the patient there for a couple of days of testing does not mean quality face time with physicians.” Dr. Hyde’s overall point was that unless people are paid for doing work, they won’t do the work.
Another point made was how a patient presents to the doctor. It is a quick judgment call on the part of the physician, but the stature, walk, dress, and speech of the patient goes into a quick sizing-up. If the patient is complaining of vague symptoms (most people with ME/CFS tend to be vague), many doctors jump to the “obvious” and easy diagnosis of a psychiatric condition and can be dismissive of the patient.
In an effort to improve medical efficiency
In an effort to improve medical efficiency, many physicians now run between multiple examining rooms, see patients between 6-8 minutes, and whether conscious of it or not, limit patient questions and dispense with time-consuming, proven patho-physiological diagnosis.
It takes too much time to counsel patients rather than prescribe a pill. Some physicians have limited the number of complicated patients and/or decreased procedural referrals such as EEG, Brain SPECT, transcranial doppler, tilt table test, CAT scan and MRI testing.
Many physicians use templates in their notes such as SOAP― S. subjective: history of present illness; O. objective: prior diagnosis, new examination; A: assessment: diagnosis; P. plan: tests, referral, advice or treat. As Dr. Hyde pointed out, this is part of the educated-guess diagnosis.
In the 1890’s, another Canadian, Dr. William Osler, became the chief of John Hopkins Hospital, Baltimore, MD. Osler’s technique was to find the cause of the illness and then treat it specifically, which was regarded as being revolutionary at that time.
Doctors to this day rarely look for the causes of illness. Dr. Hyde emphasized that he himself has never had ME/CFS patients with only one thing wrong with them; instead, patients can have 10 to 20 underlying problems.
ME/CFS breakthroughs—or maybe not
In September, 1990, Drs. Elaine DeFreitas, David Bell, and Paul Cheney were pictured on the cover of The CFIDS Chronicle because they were on the forefront of ME/CFS research at the time. People believed that Dr. DeFreitas had found a retrovirus associated with the illness and her work was promoted as a research breakthrough.
Drs. Bell and Cheney, each having found themselves in the midst of an epidemic outbreak, began treating numbers of their patients.These doctors were well known and lent credibility to the illness.
Dr. Hyde, with his forensic background, explained that researching the cause of a virus in an outbreak can only be done if you go to the epidemic and look for viruses in everyone. Otherwise, there is no way to tell what caused an outbreak because healthy folks carry around so many viruses that don’t make them ill―scientifically, this research did not have the significance implied.
Though it proved to be quite challenging, Dr. Hyde was determined to find out how research funds earmarked for ME/CFS had been spent by the National Institutes of Health (NIH), Bethesda, MD. After many calls to NIH, he was told he would have to call each department individually to inquire where the money was directed.
Much of it went to a study on alcoholics who were thought to be fatigued. More was spent on cancer patients who were thought to be fatigued. The misspending of CFS research funds also occurred at the CDC, a circumstance that was eventually made public by a whistle-blower, the head of the CFS research programs at the CDC.
Dr. Hyde stated that he felt Dr. Stephen Straus, who headed up the ME/CFS research at NIH, was “the bane of the problem”. Dr. Hyde then laid out his case for his statement explaining that in a time-line, the term CFS was first employed by Dr. Straus in 1986. In 1987, Straus believed CFS was caused by Epstein Barr Virus (EBV). In 1988 his term CFS was used to label the new CFS Working Case Definition. Keep in mind that ME was an established illness in other parts of the world. Dr. Straus maintained a very poor attitude towards ME/CFS and given his position at the NIH, this had a negative outcome on patients and research for many years.
Dr. Hyde then went on to discuss how some players in the ME/CFS field were just making money on unproven lab tests, as was corroborated with the downfall of the XMRV theory. He discussed how researchers, laboratories and pharmaceutical companies would put more effort into a project if it proved money-making as in the case of utilizing something with a patent on it. ME/CFS progress suffers when research is steered by power or towards profit or when results are overplayed.
Enterovirus in ME
According to Dr. Hyde, there have been multiple epidemics, since 1946 to the present, in which an enterovirus has been recovered and associated with development of ME. An enterovirus has a certain structure/mechanism, but there are many types included in enterovirus group (i.e., polioviruses, non-polioviruses, coxsackieviruses, echoviruses). These outbreaks have been reported from around the world and a majority of them seem to occur in institutional settings such as schools, hospitals, residences and after congested travel or being in close quarters.
Dr. Hyde has personally researched all the outbreaks for decades. In discussing what may cause ME, he brought up the fact that in 1992 The Nightingale Research Foundation had sent 100 blood samples (from 60 gradual and 40 acute onset ME patients) to Drs. Galbraith and Nairn at Ruchill Hospital, Glasgow for enteroviral studies.
50% of acute onset patients were positive for chronic enterovirus infection, but three years later few patients were positive. None of the gradual onset patients were positive.
Dr. John Chia, an infectious disease specialist and Assistant Professor at UCLA in Los Angeles, CA has been finding enterovirus in the biopsied stomach mucosa of ME/CFS patients in 82% of the patients. Currently, there are no significant treatment options for enterovirus, but Dr. Chia is currently testing out some medications.
Dr. Hyde mentioned he had recently spoken with pharmaceutical companies about medications for enteroviruses, but there seems to be nothing currently in the pipeline. He also believes some of the problems lie with the fact that there are no patents on enteroviruses, and therefore no financial motivation.
If by chance you, as a patient, had a stomach biopsy, and it was stored in a paraffin block, not a fixed specimen, you may be able to get 3 slices and have it sent to Dr. Chia for testing. You would have to contact Dr. Chia for information. Specimens stored in a paraffin block will last forever, according to Dr. Hyde.
Dr. Hyde drew a contrast and similarity between refugees and ME/CFS patients. He showed pictures of 2 women from Iran with similar names. The first one was killed and images uploaded to the internet. However, Iran went after the second woman, thinking they were one and the same and attempted to murder her. She was a university English professor, who was forced to flee for her life from Iran. She escaped from being killed, but wound up in a refugee camp in Germany and wrote “Every day in such a place is torture, not just for me but for all those refugees. Some had been there for 10 years. You give up on your own destiny. You have to submit to whatever the system decrees. In my society I had achieved so much and now I had nothing—I was in a drawer, a folder labeled 'refugee'." Her name is Neda Soltani. Dr. Hyde made the comparison of her plight and that with patients who feel pretty much the same way.
1934 Los Angeles ME epidemic
Dr. Hyde had the opportunity to examine two physicians who had become ill during the 1934 polio epidemic outbreak at the Los Angeles (LA) County Hospital. According to Dr. Hyde’s slide, 198 healthcare workers, who were immunized with sera from recovering patients, fell ill with ME, but not polio.
He believes in this case that the combination of an immunization and viral infection triggered their ME. The two doctors sued the hospital and the city of LA and received about 2 million dollars each.
Dr. Hyde’s hypothesis is that this was a wake-up call for insurance companies to dismiss the illness and from then onward, anything resembling ME was mocked. There were times then, and even now, where ME patients were put into psychiatric hospitals and labeled as crazy (plus they were given drugs that made them sick). So, when CFS came along, it seemed to follow the same pattern. Same illness, different name, same outcome.
Pseudo-Diagnoses are non-scientifically-testable diagnoses
In explaining what he meant by pseudo-diagnosis, including anything with the word “syndrome” or “disorder” after the name, Dr. Hyde said that the following syndromes are diagnosed on symptoms alone without any available diagnostic laboratory tests:
- CFS, CFIDS
- IBS (Irritable bowel syndrome)
- Non-major depression
- Hysteria, conversion or somatization disorder
His analogy was akin to having a headache but not knowing if it was caused by a migraine, brain cancer, or perhaps an injury to the neck, but the only thing the headache did was indicate something was wrong and should be evaluated. He emphasized that anything with the name “syndrome” or “disorder” means it is something that should be looked into.
Conversion Disorder is a situation where the patient has physical symptoms with no organic cause. It affects motor & sensory functions.
Somatization Disorder affects the gastrointestinal, nervous, cardiopulmonary, or reproductive systems.
Disorders with hysteric features typically begin in adolescence or early adulthood.
Immunizations and ME/CFS and FM
Dr. Hyde emphatically stated that “immunizations save lives, and are better than all the doctors in the world put together”, but cautioned that doesn’t mean they are problem-free. His concern centered on two: recombinant hepatitis B immunization and the rubella immunization.
Dr. Hyde also spoke to the issue of contaminated immunizations around the world and how they can possibly trigger ME/CFS/FM illnesses.
Recombinant hepatitis B immunization
He has personally seen some very ill, bed-ridden patients as a result of the recombinant hepatitis B immunizations, causing disautonomia―the disconnect between the brain and the ability to maintain normal pressure in peripheral arteries.
Dr. Hyde explained how the rubella immunization can cause rheumatoid arthritis. If a pregnant woman has not had the vaccine, she cannot receive it while pregnant because it will cause harm to her unborn child.
When Dr. Hyde started in practice, the current wisdom of the day then was to give the immunization immediately after childbirth to both the mother and child. If the mother was breast-feeding, a sensitivity to, not immunization from rubella would develop in the child.
If the child was a boy, nothing happened to the child.
If the child was a girl, and she received a booster for that vaccine in grade 8 (in Canada), she could go on to develop an internal auto-immune reaction which then could develop into rheumatoid arthritis. Dr. Hyde pointed out that this is 12-14 years after the initial insult to the body.
Dr. Hyde discussed some of the issues around immunizations that have been contaminated and still go to market. For example, during 2004-2005 some batches of the flu vaccine manufactured by Chiron Labs in England became tainted with Serratia Marcescens.
The US and Canada bought vaccines made in England because they were cheaper. Even though the company informed the buyers about this contamination, the US and Canada continued to use the immunizations for 6 more months. Dr. Hyde feels many people probably got ill with ME/CFS after this.
Immunization and travel start date
Dr. Hyde emphatically told the audience that when preparing for travel abroad, particularly following and during trips to third world countries, “NEVER get an immunization and then travel immediately. Always allow 30 days between the injection and the travel plans to allow the immunization to take effect.”
He explained that if, by chance, you got on a plane the week following the immunization, and sat next to someone with a minor virus, your immune system may not be able to fight it off and you could end up becoming chronically ill with ME/CFS.
A virus plus an immunization do not mix well. He reiterated that acute ME is usually not detectable by routine examination and only a SPECT, BEAM or PET scan can pick up the encephalopathy.
What questions should a doctor be asking?
Dr. Hyde shared his thinking that all doctors should be asking themselves the questions “what makes the symptoms worse, what makes them better and how did it start,” having learned these basic skills in medical school.
Other questions to ask are if there was any injury to the physiological system, could it be proven which organs were injured and in what manner?
The theory is that if a patient is ill, there must be proof of it.
However, the physician has to be thorough enough and ask the right questions to determine which tests to run and how to interpret them. This is where many ME/CFS and FM patients fall through the cracks.
Above all, Dr. Hyde stressed that it is absolutely important to capture a patient's genetic history, beginning from their infancy to the present. Before he does anything, he will spend the first visit (which usually takes 1 1/2 days) gathering patient background information.
Dr. Hyde’s protocol of taking a patient history and work is as follows:
- Genetic History
- Historical Illnesses & Traumas
- Immediate Prior Illnesses or traumas
- Trigger (any combination of infection, immunization, medications, trauma, surgical procedure, transfusion, severe emotional injury)
- System Injuries or Pathophysiological Injuries
- Multiple Organ Injuries
Myalgic Encephalomyelitis vs CFS
Dr. Hyde stated that he did not think ME and CFS were the same thing and the names should not be used interchangeably. He noted that he did not agree with the effort in the U.S. to combine them.
He also made a distinction between the gradual onset of ME and the sudden onset of ME. Dr. Hyde felt that patients with a gradual onset were easier to treat, as there usually was an identifiable cause and treatment.
In contrast, those with a sudden onset were much more complicated and showed the encephalopathy in the brain. He concentrated his talk on sudden onset of ME.
Dr. Hyde’s definition of ME
Take the term apart and it means: My: muscle; Encephalo: brain; Myel: spinal cord; itis: inflammation. ME is a measurable, diffuse, patchy, chronic patho-physiological brain injury. He defined ME as:
- A previously well individual who has developed a new incapacitating, chronic cognitive, intellectual and physical illness.
- Characterized by rapid onset and persevering cognitive and physical exhaustion following normal physical, intellectual, sensory, or emotional exposure or stressors.
- Patients are frequently women, healthcare workers, teachers and students.
He stated that classical ME cannot be seen on an X-ray, but can be caught on a SPECT scan. Dr. Hyde explained that when sent for the scan, the patient should be exhausted and at their worst so the test will see the brain at its worst.
In contrast, the MRI is an anatomical map of the body while the SPECT scan is functional (meaning how the brain is actually working). This diffuse injury destabilizes the central nervous system control of many body functions.
There were slides presented from Dr. Hyde’s medical text book, authored in 1992, The Clinical and Scientific Basis of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome. The scans done by Xenon SPECT (the Xenon machine is no longer made) of a 37-year old female ME patient showed abnormal resting SPECT; post-exercise SPECT that still shows abnormal findings; and a 24-hour post-exercise SPECT also showing abnormality even though the patient had not exercised since the initial time. So the brain continued to show a break-down of functioning.
These findings were demonstrated by Drs. Jay Goldstein and Ismael Mena at UCLA in 1989. Dr. Hyde found it unbelievable that even today the SPECT test is not widely used.
Dr. Hyde made clear that the SPECT scan showed exactly what an acute onset of ME in the brain looks like if caused by encephalomyopathy. What was so interesting was how he explained how most patients would perceive the situation―they may think they just have a headache with no idea they have an encephalopathy. Only a SPECT scan or spinal tap would show it at the time of onset.
A slide of a 10-year old child’s ME brain showed marked (50%) decreased blood perfusion in the right frontal and right posterior parietal and occipital lobe. (Slide courtesy of Drs. Michael Goldberg & Ismael Mena of California.)
Dr. Hyde presented another slide — this time of a basal ganglia in the brain. A second slide, taken two years later, showed the left side of the basal ganglia just starting to return.
After following patients for decades, Dr. Hyde noticed a correlation between male patients that had ME for almost 25 years and the increase of Parkinson’s disease. Although he does not know what the connection is yet, he thinks there has to be a relationship between ME and Parkinson’s disease.
In explaining some of the various other diagnoses he found in “diagnosed” ME patients, Dr. Hyde listed quite a number, driving home the point that doctors MUST really examine these patients. Some of the missed diagnoses included but were not limited to:
- Central Nervous System Vascular disease
- Carotid/Vertebral disease
- Coronary & Heart disease
- Peripheral vascular disease
- Autonomic diseases
- POTS, Ehlers Danlos, Marfan
- Clotting Factor disease
- Endocrine system disease
- Multiple Sclerosis
- Renal & Hepatic disease
- Syphilis, Lyme, Brucellosis, TB
- Von Economo-like
- Metal & chemical & medication poisoning
Dr. Hyde mentioned that he has found type-1 diabetes and blood malignancy in some of the patient’s family members from the outbreaks and thinks family members should be further studied. Dr. Hyde has authored another book titled Missed Diagnoses.
The majority of Dr. Hyde’s patient load came from students, teachers and healthcare workers. He said the worst affected group was the respiratory therapists, who were coughed on all the time. He stated that 60% of post-viral ME occurs in the above population as well as folks following or during trips to third world countries.
Most epidemics occur in institutional settings such as schools, hospitals, residences and after bus or air travel in close quarters. Some ME cases are associated with immunizations, which he already covered.
Presentation on Fibromyalgia (FM)
Dr. Hyde asked the audience if any of them with FM knew the exact cause of their illness: viral, bacterial or genetic?
As a fun start for his Fibromyalgia patients, Dr. Hyde sends them with a camera to a museum that has a thermogram. This type of picture will show blood circulation in the body, or, as is the case with many FM patients, it will show lack of circulation, which is Raynaud’s disease. Patients get cold easily and don’t warm up, and in extreme cases, can go into hypothermia.
Dr. Hyde’s definition of FM
FM used to be called Fibrositis, a non-articular muscle pain. Arthritis affects the joints. A patient can have both FM and arthritis. Fibromyalgia is non-articular muscle pain. Arthritis is articular (joint) pain.
If you have pain in the joints, in the bones, inside your chest or abdomen or pelvis, that is not fibromyalgia. Fibromyalgia is muscle pain.
Dr. Hyde's view is that Fibromyalgia is a vascular pathology — a pathological, hyper-elasticity of the peripheral vascular system or anything that causes this pathological expansion. Translated it means a problem in the muscles of the blood vessels.
At this point he asked everyone in the audience if they could touch their tongue to their nose. If so, it was evidence of the hyper-elasticity of the interstitial tissue called Ehlers Danlos Syndrome. In explaining its meaning, he said the ascending aorta can become flabby and have problems pumping blood. It was suggested that anyone who can meet this test should ask his/her doctor for an echocardiogram looking specifically to check the ascending aorta.
What makes FM worse
There were several answers to this question. Dr. Hyde started by explaining that a patient can expand his/her vascular system simply by eating salty potato chips and drinking beer. If the patient feels worse, it is a good chance they have FM. That is because as the vascular system expands in the arms and legs, it causes increased pain to the patient.
If, however, the patient feels better after ingesting the chips and beer, Dr. Hyde said they may have dysautonomia. Dysautonomia (autonomic dysfunction) is a broad term that describes any disease or malfunction of the autonomic nervous system.
This condition is common in ME/CFS patients resulting in Neurally Mediated Hypotension (NMH), Orthostatic Intolerance (OI), or Postural Tachycardia Syndrome (POTS) diagnoses.
Most FM patients do not drink alcohol because of their negative response to it.
Dr. Hyde suggested an even better way to worsen Fibromyalgia is to do a Persantine Myoview Stress test. This is a chemical stress test which instantly expands the blood vessels causing significant, even intolerable pain in FM patients.
A physician who administers this test has a drug that reverses its effect. Sometimes the patient has immediate relief, and sometimes it might take a week or so for the patient to get back to pre-test baseline.
Causes of FM
A better question is, “What causes this condition?” Dr. Hyde offered 3 suggestions:
- Central Nervous System (CNS) injury of the arterial messenger system
- genetic disease
- autoimmune or chemical injury to the arterial wall’s succinyl choline receptors.
In diffuse encephalitis, the brain, which produces the hormones that tell your blood vessels to contract, has been injured by the kind of encephalopathy that ME-type patients or acute onset ME/CFS patients have.
Dr. Hyde thinks FM is a central nervous system injury to the arterial messenger system.
CNS injury to arterial messenger system as an FM cause
It is also possible to have secondary Fibromyalgia, which can be caused by injury to spinal vertebrae and its appendages. Nerve endings for the entire body come out of the posterior tracks of the spinal cord.
Dr. Hyde thought it is very important for FM patients to have an X-ray of their entire spine, not just the anterior and posterior views, but also the oblique views. His reasoning was the patient may not have FM even though they have all the symptoms of FM, but instead have an injury to the nerve endings in the spine that pick up pain as they exit the spinal column.
Dr. Hyde went on to say that this could be genetic, but it could also be delayed injuries from an auto accident. In a seemingly minor motor vehicle accident, the neck can become hyperextended, causing the spinal cord to hyperextend and cause all the small capillaries that feed the bones in the spine to be ripped out.
Insurance companies want to settle quickly, especially if there are no broken bones. Dr. Hyde said “You should never give up your rights to sign away claims. What happens is that 5-10 years later there can be disintegration of the micro-arterial capillary system of the spinal bones, which causes arthritis and also FM.”
Genetic and auto-immune diseases as FM causes
Dr. Hyde raised the issue of genetics and why it is important. For example, HLA B27 is simple blood test, which when positive, indicates an increased risk for development of certain illnesses.
HLA B27 is associated with Ankylosing Spondylitis and with Psoriasis, with or without arthritis.
Dr. Hyde even went on to further say “that if family members have psoriasis, and you don’t, you stand a very good chance of developing Fibromyalgia.” He feels genetics definitely play a part. The reason it is so important to have a good family history of the patient is because illness that develops 10-20-30 years later could possibly be traced back.
This is an example of why it is so difficult for doctors to figure out. Some other genetic illnesses are: Hyper-extensibility syndrome, Ehlers-Danlos syndrome, and Marfan and Marfan-like syndromes.
Some auto-immune causes of disease are Lupus Erythematosus, Sicca syndrome (the milder form of dryness of eyes and mouth) and Sjögren’s syndrome that has chronic drying of the eyes, mouth and vagina. In the most severe cases, Sjőgren’s can be a serious rheumatoid-like illness and it can cause death. Raynaud’s disease, rheumatoid arthritis and Rubella immunization have already been mentioned. Dr. Hyde did not speak to every auto-immune illness, but touched on the most common causes of what he believes to trigger FM.
In his earlier discussion about immunizations, Dr. Hyde described how the rubella immunization, more specifically, the booster shot could trigger an internal autoimmune reaction in females and lead to serious rheumatoid arthritis. Often, the initial insult to the body can occur a decade or two earlier, but doctors only sometimes make the connection.
Dr. Hyde isolated the medications/worst offenders that can cause pharmaceutical injuries to muscle, its innervations and its constituents:
- Quinolones (Cipro), Minocycline
- Loss of or stopping of estrogens
- Thiazide diuretics
- Multiple Herbal Medications: Alfalfa
Side effects of many medications can cause illness. Dr. Hyde feels that both the physicians and the pharmaceutical companies share some responsibility in this happening. The pharmaceutical companies want to sell product and the doctors want to prescribe.
He gave an example of Lupus-like symptoms being caused by a drug. He said that logic would indicate that if you stop the medication, the Lupus symptoms would go away. However, Dr. Hyde cautioned that has not always been his experience.
A slide was shown listing a small number of the hundreds of medications known to cause side effects triggering FM or FM-like illness. Dr. Hyde went through the list explaining each one.
He first started with Statins saying, “They were one of the biggest causes of FM symptoms”. Statins are an anti-cholesterol medication, and will usually melt the muscle, a process called rhabdomyelisis. One of the well-known side effects of statins is muscle pain. Anyone on statins should have a creatine phosphokinase (CPK) blood test every 3 months, as it will show any signs of inflammation.
A slide showing the percentage of symptoms in normal, non-ME/CFS & FM patients on statins shows:
- 13% will have muscle pain
- 10% joint pain
- 8% headache
- 5% asthenia/CFS
Over 50% of ME/CFS patients on Statins have severe side effects including rhabdomyelisis.
The next category was NSAIDs―non-steroidal anti-inflammatory drugs. Many physicians prescribe NSAIDs for treating spinal trauma, FM itself, fracture, arthritis etc. Dr. Hyde said, “NSAIDS are one of the biggest causes of Rheumatoid-like Arthritis known to God and man. It kills people.”
He further clarified by describing what happened to a patient he inherited too late. She was given NSAIDs for trauma from an automobile accident and she stayed on them continuously for over 8 months. During that time, she became deaf, chronically constipated, and ultimately died.
Dr. Hyde explained that long-term use of NSAIDS can destroy muscle, cause inflammation of the arteries, and kill the blood vessels. His patient had developed the chronic constipation because the arteries going into the intestines and kidneys were killed off, the deafness was caused by the NSAIDs, and by the time she came to him as a patient, there wasn’t too much he could do for her.
Over the years, many of the ME/CFS & FM specialists have mentioned that NSAIDs may make the symptoms worse. Dr. Hyde just clarified why.
Cipro and Minocycline
Cipro and Minocycline are antibiotics. And although Cipro is an effective medication, Dr. Hyde said “Cipro should never be taken longer than 30 days, and, it shouldn’t be given to children because it will rupture their tendons.” Long-term use of the drug in adults can cause the same issue. He felt Minocycline would not burst the tendons, but can cause FM.
Estrogen was widely used by many women for years then was stopped because of the concern over breast cancer. Dr. Hyde thought there was more of a risk eating a lot of chicken because they were loaded with estrogen, than taking the estrogen pill. He casually commented that if a man was having trouble performing, it could be due to too much estrogen, usually from a food source.
Thiazide diuretics and alfalfa
He did not spend much time on Thiazide diuretics but mentioned that they, along with alfalfa, which is in many medications and used in herbal preparations, can cause symptoms. He stressed that patients should ask for a referral to a physician who knows a good deal about medications and interactions, most likely a psychopharmacologist. If at all feasible, the amount of medications taken should be reduced.
Dr. Hyde mentioned that patients can always have their list of prescriptions and over the counter pills checked by their pharmacist for interactions. The pharmacists have access to a special computer program of drug interactions that many physicians do not have.
No doctor could possibly know all drug interactions. Dr. Hyde made clear that FM is not a disease, but can be any of the above conditions as well as many not listed.
Questions & Answers
Q1) Is an annual flu shot a good idea or a bad idea for an adolescent with ME/CFS?
A: For an adolescent, the dosage of mercury alone every year is really, really additive and can cause brain injury in some people. Folks over 65 years old don’t usually seroconvert to flu. It is given to everyone, especially in nursing homes, to prevent the spread of flu but it doesn’t help the patient. Almost any immunization given to a person over the age of 65 won’t seroconvert, meaning they won’t build up antibodies adequately. A few people might, but not sufficiently. I’m not one for flu immunization. I’ve seen too many bad things.
Q2) US groups are trying to combine ME & CFS and code them the same―what do you think?
A: They are not the same. Chronic Fatigue Syndrome was invented by Stephen Straus who thought he had Chronic Fatigue Syndrome when he had a brain tumor. You have to examine these people. I think the only way you can diagnose ME is you do a brain SPECT when the patient is tired. It is as simple as that. If their brain looks perfect, something else is causing their fatigue. It’s not a brain injury. ME is only diffuse brain injury. Chronic Fatigue Syndrome can be anything from that list of things on the slide I showed you before. Anything, plus another 100 things that are not on those lists. When I am doing a report for disability insurance, even though everyone has free medical in Canada, I never mention the word ME. I never mention the word Chronic Fatigue Syndrome. I never mention the word Fibromyalgia because the lawyers who are working for the insurance companies have all these experts who come and say, “Oh, everyone knows that Chronic Fatigue Syndrome is a minor psychiatric disease and the people can really work.” So, you never mention that and you go to the heart of the matter and you go and say what is really wrong with these people.
Q3) If acute onset of CFS and ME causes brain damage, what type of treatments might help?
A: Well, I’ve mentioned that Dr. Chia, has had good success in finding the enterovirus in the stomach mucosa of CFIDS/ME patients. We’re just starting to use treatments that Dr. Chia has been using. That’s skeptical at the moment. I just don’t know. All I know is there is no good anti-enteroviral medication in existence at the moment. There are a lot of things I don’t know how to treat. One thing I have noticed in ME is people with money get better faster. And it is not because they have access to physicians. What it is— they have a cushion. I’ve had a lot of doctors come down with severe ME and diffuse brain injury after that epidemic period, and those with insurance stopped working, were able to relax, had money coming in, were able to live a healthy life, weren’t under any stress, their mortgages weren’t being taken out from underneath them, their spouses didn’t run away, everybody was happy, the kids were happy, and they got better. Not everyone, but most of them to some degree. None of them became 100% better. The doctors who were saying “Oh, God, I’m only 35. What do I need health insurance for, disability insurance” and didn’t get insurance, and they’d just graduated [from medical school] and they came down with that epidemic, not one of them, not one of those doctors is working today. Several of them committed suicide—they didn’t get better. After you fall ill, the ability to do nothing except relax and live a healthy life, gives the body a chance to fix itself. There is no better physician than the body.
Q4) Thoughts on any of the following treatments that I read about that some people are trying: Imunovir, low dose naltrexone, antivirals?
A: You have to investigate the patient thoroughly to find out why they are ill and know what you are treating.
Q5) What is POTS?
A) Postural Orthostatic Tachycardia Syndrome is one of the classic dysautonomias. We see it most commonly after the recombinant hepatitis B immunization. We have 200 patients I mentioned earlier with POTS. What is POTS—your heart rate, which should be running around 60-80 beats per minute, should drop to 45 beats per minute when sleeping. What happens with POTS people when they’re sleeping, is that their heart rate may drop down to 55-60 beats per minute and then when they awake, and try to move or do anything, their heart rate rises to over 100 beats per minute, which is tachycardia, or close to it in the 90’s. If they get excited or if they try to do anything their heart rate may instantly go up to 150 to 200 beats per minute. If you put them on a treadmill, their heart rate can go up to 300 and you have to stop them. POTS is a major consequence to several other conditions. One is a brain injury, and injury to the system regulating the pressure in the blood vessel. I spoke about it earlier, I just didn’t use the word POTS.
Q6) I had acute onset of ME 1990 after a bout of pneumonia—had years of recurring infections. Now, in 2012, diagnosed with Sjőgren’s (via positive salivary gland biopsy), joint enlargement deformity/pain—worsening of dental issues with tooth loss. Do I have autoimmune disease replacing ME? Both?
A: Of course you do. Forget about the names ME, CFIDS & FM. Ask what is causing this real symptom. You can’t run off and have a test. You have to have a total body examination.
Q7) How do you do a workup?
A: I’ll try to send to your group my working profile and you may even want to publish it. It will give you an idea of how extensive my exam is. We do Skype interviews with patients for 2 hours and sometimes we can help them.
Q8) Is a TB test a good idea?
A: We do a tuberculin skin test on every patient. We have picked up 5 cases of TB among people who think they have CFS. And it is so simple to do. It is a little skin test, costs nothing, put a little bleb underneath the skin. If the next day you have a big red reaction, you may have TB. You could have other diseases which could blow up.
Q9 ) I have very high heavy metal toxicity after EDTA & DMPS chelation. I have become much worse with my ME & FM. Your thoughts on this?
A: This treatment really doesn’t work. I don’t know a treatment that works. The idea of chelation has made a lot of people rich in Canada and the United States. What happens with heavy metals toxins is it goes in the brain. We had some serious injury to farmers when I was working in Glasgow for a short period of time. The doctor was doing every test he could on these farmers. We found exposure to different kinds of pesticides, herbicides and metals, but nothing special. They put them through chelation and all sorts of things. There was nothing we could really prove until they died. When they died, we got their brains and the brains were so solid with mercury, pesticides and herbicides that I phoned the Mounties, our national police force, like your FBI and CIA combined, and asked, “If you wanted to murder your husband with a nice milkshake of herbicides and pesticides could you tell?” They said, “We can’t.”
Q10) How does POTS contribute to CFS?
A: It doesn’t contribute. POTS patients have it the worst. The POTS and autonomic nervous dysfunction people are so terribly ill—those are the ones that are not usually here. The better POTS patients might be here, but the serious ones are home in bed right now. They don’t even know there is a Massachusetts organization to help them.
Q11) What can you tell us about the relationship to gender and CFS/ME?
A: I mentioned earlier about the difference between RA and girls and boys. Boys don’t get it and the girls do. What you are looking at with women is that they have a very different immune system. 80% of the all of the ME/CFS type patients are women. 80% of all of the MS patients are women. 80% of the RA patients are women. They have an immune system that is organized so that when they get pregnant they don’t reject the baby as an autoimmune reaction. Their immune system shuts off as part of their natural reproductive ability to develop and build a healthy child. They already have an immune system which shuts off and starts on its own, so they are more vulnerable to any autoimmune disease and most of the CFS diseases that we have talked about are highly related to the autoimmune system.
Q12) Are women who had children more likely to get ill?
A: I don’t know. I’ve never done the statistics on that. The last time we did statistics was around 15 years ago when we were looking at patients after the epidemic period of 1984 and that is one question we didn’t ask, and that would have been a really useful question.
Q13) What’s the difference between acute ME & CFS and gradual onset?
A: ME is a diffuse brain injury that is measurable. If you can’t measure it you don’t have ME. CFS depends on whether the onset is acute or gradual—if acute, it can be a combination of genetics, immunizations, medication, viral infections, things you can’t always prove, trauma, brain injury. It can be a combination of things.
Q14) Can you explain more about gradual onset?
A: Gradual onset patients are one of the most interesting sub-types of CFS because it almost always is something which is building in the patient. Those patients are the ones we find cancers in, those are the ones we find organ injury in, but those are the ones that are often best treatable. But you have to find out why.
Q15) What’s the difference between acute and chronic?
A: Most people who have acute onset ME get better. If they are not better within a year, they lapse into what we would call chronic. And very few of those people get better. On their own, probably 25 % of that group does get better. But that still leaves a large percentage of patients that don’t get better. You have to stop thinking in terms of ME, CFS and FM. You have to ask what is causing my Chronic Fatigue Syndrome. That is absolutely essential. If you can answer that question you have a chance of curing the patient.
Q16) Did you have the polio vaccine before getting polio?
A: I fell ill in grade 8 so I must have been around 11-12 years old and that was 1948. The vaccine came out in 1954-55. But even before the vaccine was introduced in 1954, it had been tested on people in the island of Newfoundland and in the island of Granada, and it killed pretty well everyone they gave the immunization to. So the vaccine was withdrawn and retooled. It was reintroduced somewhere else and it didn’t kill the people and ever since it has been the safest immunization known to God and man. It was a wonderful invention.
There had been a high risk of having your child die from polio. You hear about all the paralysis, but not about the deaths. Most of these kids died. It was also mainly women who died, not kids, but you didn’t hear about those statistics because there was no research money for women in those days. Money was easier to get if children were being studied. I don’t know if any of you remember Little Jimmie, the March of Dimes advertisement. Even then, women would give money for the study of children. Only later did the advertisers bring in a girl.
Q17) Is medical cannabis an option for replacing other meds?
A: I was on the medical committee in Canada, the LeDain commission, which looked at the safety of drugs. The LeDain commission came out showing that marijuana was not dangerous at all. Medical cannabis depends if you are taking it by a pill form, inhaling it from a cigarette or taking it internally as in the wild stuff. All my friends who grow cannabis are as ill as can be physically. And they smoke it all the time. Does it help you sleep? Yes, it does—so does cocaine. So does morphine. Do you get good sleep? Anything you inhale into your lungs is causing you major, major damage. I’m not one for cannabis.
Q18) Do you win when you go up against American insurance companies?
A: We almost always win. It is not because we’re good; it is because of what we do.
Q19) How do you afford to practice medicine?
A: I make an average of $40,000 a year in medicine. Every now and then I buy a property and sell it at a ridiculous price 5-10 years later and make a couple of million dollars. It is easy to make money but it is boring. But in medicine I just like to try to figure out what is wrong with people and that is a lot of fun. We charge a lot of money to see American patients, about $10,000. But then we do all the testing in Canada which costs about $6-7,000. The Canadian patients are only charged about $3-4,000. However, it still takes us 18 months to investigate them and we do a better job than any of the big American clinics.
Q20) How do you win against insurance companies?
A: Insurance companies are really easy to beat if you know what is wrong with the patient, and these patients are seriously ill. We have done about 2000 patients since 1984 and most of them were in the early years. Now we take much longer per patient and only take about 20 new patients a year. They are easy to win because the patients are so ill. The cases never go to court because the insurance companies settle.
You can learn more about Dr. Hyde at www.nightingale.ca
You can learn more about Dr. Chia at the Enterovirus Foundation
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Notice about names
The Massachusetts ME/CFS & FM Association would like to clarify the use of the various acronyms for Chronic Fatigue Syndrome (CFS), Chronic Fatigue & Immune Dysfunction Syndrome (CFIDS) and Myalgic Encephalomyelitis (ME) on this site. When we generate our own articles on the illness, we will refer to it as ME/CFS, the term now generally used in the United States. When we are reporting on someone else’s report, we will use the term they use. The National Institutes of Health (NIH) and other federal agencies, including the CDC, are currently using ME/CFS.
Massachusetts ME/CFS & FM Association changed its name in July, 2018, to reflect this consensus.