Hi Scott,
I am less convinced now that the fat metabolism lies at the origin. Instead, EBV infected cells secrete cytokines and chemokines as well as inhibitory cytokines. This may lead to subtle and less well understood immune defects, such as cytokine imbalance. I think here we arrive at the heart of cellular immunity. This Chapter Opening under the link explains. As you may see from the article, the immunological defects underlying EBV infection are not well understood.
http://informahealthcare.com/doi/abs/10 ... 014280.018
When the cells are in an emergency (in our case because of the virus attaching to e.g. its membranes), they may shed some AA in parallel to the cytokines. Biologically seen, this would make sense as it would help the cell because the internal balance of structural proteins would change towards anti-inflammatory ApoA1. Where I don’t exclude that the immune meta-system, besides being triggered by the parallel secretion of cytokines, has learned over the millions of years of evolution to recognize the AA leak as a sign that there is something wrong with the cell. The above thesis would need to be amended a bit accordingly.
Understanding the enormous complexity of our microcosm will be a daunting task. Notwithstanding, I think for all patients with MS the foremost important thing is to get the EBV virus down. Where there may be various possibilities for recovery, including stem cell therapy, liberation from ccsvi, strenthening CD8+ T-cell immunity etc, without getting the virus down the other therapies are unlikely to have a lasting effect.
To knock the virus down, there seem to be various options including vaccination, antiviral (e.g. Letermovir, Raltegravir), and chemo (e.g. Rituximab). Also what prof. Pender is doing with adoptive immunotherapy is very interesting in this regard.
The fascinating article under the link below sets out the EBV-infected autoreactive B-cell hypothesis which overlaps or complements with what we have seen here including on the development of meningeal B-cell follicles causing damage to the underlying cortex. What seems to be needed now is a team of experts who amalgamate the EBV-infected autoreactive B-cell hypothesis with our own thesis on MS.
http://www.nature.com/cti/journal/v3/n1 ... 1425a.html
After a long journey of 4 years, I feel fairly comfortable that here we have the right focus for finding the solution and a real cure for MS.
Leo
Theoretical Immunology
This Is MS
MS is a two stage process – the double peak in the graph of age of onset which is a relatively amorphous thing by itself provides an indication.
In the first phase, the virus spreads in meningeal follicles, the lymphatic system and stem cells. Every now and then, receptors get blocked, you get an acute relapse, the immune system removes the infectious agent, and you see remission (RR).
But as the virus spreads, more and more cells in particular stem cells like OPCs get infected and become transgenic. People with transgenic cells are healthy but predisposed.
As of mid age, another phenomenon kicks in. The virus has spread so far that increasingly B-cells get infected with a lack of sufficient T-cell function to contain B-cell replication. As B-cells cross-react with transgenic cells (common epitodes), a lot of damage is done and the typical MS plaques show up (ccsvi is a factor here).
The neurological path is weakened and because of that any new problems with receptor blocking which were not sufficiently severe before to get diagnosed will now result in more severe symptoms and one gets diagnosed. At this point the progressive mechanism is already underway and one will be generally worse off.
There will be a lot of fall out including a huge oxidative stress with all sorts of secondary effects. Over time, as the virus and the effects of the oxidative stress spread, more and more tissue will get affected leading to a dysfunction of the endothelium in larger parts of the body.
In its very essence, I believe This Is MS.
The hope is that if the Chronically Active EBV can be brought under control, remission from progressive MS is possible. You can also get some form of control through the fat metabolism.
I realise that for the readers it must now all look pretty confusing. But this last posting is nothing more than an extension of the thinking that was emerging in the previous posts. In fact, the previous posts enrich the picture with all sort of details on the wider implications.
In the first phase, the virus spreads in meningeal follicles, the lymphatic system and stem cells. Every now and then, receptors get blocked, you get an acute relapse, the immune system removes the infectious agent, and you see remission (RR).
But as the virus spreads, more and more cells in particular stem cells like OPCs get infected and become transgenic. People with transgenic cells are healthy but predisposed.
As of mid age, another phenomenon kicks in. The virus has spread so far that increasingly B-cells get infected with a lack of sufficient T-cell function to contain B-cell replication. As B-cells cross-react with transgenic cells (common epitodes), a lot of damage is done and the typical MS plaques show up (ccsvi is a factor here).
The neurological path is weakened and because of that any new problems with receptor blocking which were not sufficiently severe before to get diagnosed will now result in more severe symptoms and one gets diagnosed. At this point the progressive mechanism is already underway and one will be generally worse off.
There will be a lot of fall out including a huge oxidative stress with all sorts of secondary effects. Over time, as the virus and the effects of the oxidative stress spread, more and more tissue will get affected leading to a dysfunction of the endothelium in larger parts of the body.
In its very essence, I believe This Is MS.
The hope is that if the Chronically Active EBV can be brought under control, remission from progressive MS is possible. You can also get some form of control through the fat metabolism.
I realise that for the readers it must now all look pretty confusing. But this last posting is nothing more than an extension of the thinking that was emerging in the previous posts. In fact, the previous posts enrich the picture with all sort of details on the wider implications.
Re: A new concept and treatment options for MS
Hi Scott,
There is a phenomenon that I would want to bring up. I suffer from numbness in the limbs after a night's sleep in a heated bedroom. Central heating strips the air of negative ions. Negative ions work against oxidative stress.
I think the phenomenon is best described by the term "earthing", in this case a lack of earthing. Sinatra in his book calls it a landmark idea. It also relates to the symptoms in RR.
The story then goes to nature's most abundant anti-inflammatory. Reconnecting to earth allows the transfer or free electrons into the body to extinguish the positive charged destructive free radicals involved in chronic inflammation.
Sinatra describes the positive results of sleeping on earthing mats. Quote from his book: Objective measurements showed that sleeping grounded normalised cortisol. This meant that there was less nervous system activity.
The article under the link below on Negative Ions - Vitamines of the Air also touches on the issues.
http://www.negativeionsinformation.org/ ... amins.html
Now I am not necessarily convinced about alternative practices or reconnected healing approaches. But I believe that electrically reconnecting to earth - something we have lost in our modern world - is good for everyone. My physiotherapist - a person with more that 30 years of experience in his practice - told me that people who work outside are generally much healthier. He knows, he must have seen thousands of people in his career.
My own experiences with sleeping in a heated bedroom lets me believe that there must be something there, as it is consistent and repetitive. In my own case, I think that it's the air that we breath abundantly overnight. Air heated by a central heating is rich in positive ions which according to the article under the above link acts on the endings of pulmonary afferent nerve fibers, altering the functional state of the central nervous system and through it, the peripheral organs. Fresh outside air then is negatively charged and should be healing.
Leo
There is a phenomenon that I would want to bring up. I suffer from numbness in the limbs after a night's sleep in a heated bedroom. Central heating strips the air of negative ions. Negative ions work against oxidative stress.
I think the phenomenon is best described by the term "earthing", in this case a lack of earthing. Sinatra in his book calls it a landmark idea. It also relates to the symptoms in RR.
The story then goes to nature's most abundant anti-inflammatory. Reconnecting to earth allows the transfer or free electrons into the body to extinguish the positive charged destructive free radicals involved in chronic inflammation.
Sinatra describes the positive results of sleeping on earthing mats. Quote from his book: Objective measurements showed that sleeping grounded normalised cortisol. This meant that there was less nervous system activity.
The article under the link below on Negative Ions - Vitamines of the Air also touches on the issues.
http://www.negativeionsinformation.org/ ... amins.html
Now I am not necessarily convinced about alternative practices or reconnected healing approaches. But I believe that electrically reconnecting to earth - something we have lost in our modern world - is good for everyone. My physiotherapist - a person with more that 30 years of experience in his practice - told me that people who work outside are generally much healthier. He knows, he must have seen thousands of people in his career.
My own experiences with sleeping in a heated bedroom lets me believe that there must be something there, as it is consistent and repetitive. In my own case, I think that it's the air that we breath abundantly overnight. Air heated by a central heating is rich in positive ions which according to the article under the above link acts on the endings of pulmonary afferent nerve fibers, altering the functional state of the central nervous system and through it, the peripheral organs. Fresh outside air then is negatively charged and should be healing.
Leo
Last edited by Leonard on Fri Feb 06, 2015 2:52 am, edited 2 times in total.
Re: A new concept and treatment options for MS
Dear Scott, Anonymoose, Kronk and others,
In my search for opportunities for EBV treatment, I came across the word immunosenescence and looked it up.
http://en.wikipedia.org/wiki/Immunosenescence
Now I think this may well explain why people over 60 don't get MS anymore, and why older people may stabilise at some point. The reason would be - I quote - A decline in humoral immunity caused by a reduction in the population of antibody producing B-cells along with a smaller immunoglobulin diversity and affinity.
My farther had similar symptoms than me, a limping right leg and locking knee, but he never had MS. In his late sixties, he was diagnosed with diabetes 2, lived up to his diet. He does well, his limping leg and locking knee have disappeared. Now I have always attributed his recovery to his healthy diabetes life style but I start to realise now that his age and the natural decline of humoral immunity may also have been a contributing factor.
In fact, thinking this over carefully (I need to relate things in my memory with certain events in live like the move of my parents to their new house), there is a mismatch of about 8 to 10 years between his "recovery" around the age of 60/62 and his diagnosis with diabetes 2 around the age of 70 (he recently told me how he came to get diagnosed with diabetes 2 and his age around that time). Which now finds an explanation here.
Leo
In my search for opportunities for EBV treatment, I came across the word immunosenescence and looked it up.
http://en.wikipedia.org/wiki/Immunosenescence
Now I think this may well explain why people over 60 don't get MS anymore, and why older people may stabilise at some point. The reason would be - I quote - A decline in humoral immunity caused by a reduction in the population of antibody producing B-cells along with a smaller immunoglobulin diversity and affinity.
My farther had similar symptoms than me, a limping right leg and locking knee, but he never had MS. In his late sixties, he was diagnosed with diabetes 2, lived up to his diet. He does well, his limping leg and locking knee have disappeared. Now I have always attributed his recovery to his healthy diabetes life style but I start to realise now that his age and the natural decline of humoral immunity may also have been a contributing factor.
In fact, thinking this over carefully (I need to relate things in my memory with certain events in live like the move of my parents to their new house), there is a mismatch of about 8 to 10 years between his "recovery" around the age of 60/62 and his diagnosis with diabetes 2 around the age of 70 (he recently told me how he came to get diagnosed with diabetes 2 and his age around that time). Which now finds an explanation here.
Leo
Last edited by Leonard on Mon Mar 02, 2015 8:44 am, edited 3 times in total.
Re: A new concept and treatment options for MS
I have amended the thesis a bit to take account of our latest learnings. The new part is in blue.
A new vision on autoimmunity – towards a revolution in healthcare
I am an MS patient who was trained in a technical discipline. But when I was diagnosed with MS in 2004, I became extremely motivated to unravel the disease that increasingly ruled my live and started to learn more about the disease. In the meanwhile, with my own experiences as an MS patient and the family history in mind and with the help of the vast amount of medical literature available on the Internet and some good books, some professional advice and the social and patient fora, I have become a semi-literate. The journey has led me to a new understanding of the disease that is presented here.
Paradigm changes often come unexpected and from the outside, and are motivated either by young people who are new to the field or by people who look with fresh eyes at the problem. This has definitely helped me because I did not have to unlearn, my mind was not set by old dogmatic believes that every medical student has to learn if he wants to pass his exams, and I could see new connections and concepts that others perhaps could not see, believe, accept or propose.
A critical need to open the mind set
Autoimmune diseases like Crohn’s Disease and Multiple Sclerosis (MS), in which the immune system attacks its own body rather than predatory invaders, affect 5-20% of the global community. The current scourge of immune diseases points to a growing problem of an overall weakening society. [more on scope of problem, statistics, hits ever younger people] If the trend is not changed, consequences for the general health of our population and that of future generations may be far reaching.
We must spot current trends in societal health, take these trends extremely serious and investigate what is driving them as a matter of urgency. To this end, we should question the status-quo on autoimmunity.
However, as the weight of the status-quo is so immense, every change proposal is at risk to collapse under that weight. Significant systemic problems are pervasive and hamper a course towards investigating or even considering alternative views. The risk is a stagnation while the debate does not get a fair chance and may be dead even before it has started.
In order to find a way out of the impasse, it will be critically necessary that the matter is approached with an open mind, and that alternative views on autoimmunity are explored and new connections investigated with urgency and with force.
The viral connection
The current scourge of immune disease is explained by an immune system that gets ever weaker. There is a multitude of underlying factors: an unhealthy diet (the ratio of Omega 3 to Omega 6 and satured fats drastically changed from 1:1 to 1:16, we forgot about fish on Fridays, the balance of fatty acid intake is important for homeostasis and normal development, the emergence of inflammatory diseases correlates to the evolutionary aspects of our diet), poor quality food (e.g. engrainisation, ‘hardened’ wheat, soil depletion, a lack of flavonoids which generate antioxidants, lack of earthing, hydroponic plant growth), a lack of immune system training (e.g. extreme hygiene and indoor/office life, we forgot about fasting which is deep in the Old Testament and, people who work outdoors are generally much healthier - earthing), and stress in a very broad sense.
When the immune system weakens, the herpes virus can surface [herpes is a family of viruses]. Most of the human population have it and it has been with us for millions of years, even when we were still apes hanging in the trees of Africa. But all the time it was kept in control by a good functioning immune system. However, the last 50 years, something new is happening that has not been seen before in the history of mankind [on a smaller scale: Sumeria (overfarming) and the black death (people in the upper class of society were more immune because of diet) and more recently the outbreak of diseases like the swine flu].
Our living conditions have changed so profoundly that the immune system does not keep the virus in check anymore.
The virus – host balance
The primate immune system and the herpes virus have coevolved alongside, for million of years. The fact that cytomegalovirus-like viruses are found in very many species – including in fish - suggests that it evolved along side with us even longer and adjusted itself entirely on man. In fact, humans and the virus keep each other in balance where the virus helped along the long, joint road through attack and defense to build up our present immune system.
The virus nests in the cells, and occasional breaks out and causes major changes in the immune system by the formation of highly aggressive effector T-cells (CD4 + and CD8 +). This type of immune cells for their survival depends on the presence of the herpes virus and comes in healthy people only when they are infected with the virus which itself is no longer detectable.
The relationship between the well detectable CD4 + and the CD8 + T cells and the virus means that the virus itself is somewhere in the body tucked deep inside the endothelium. The virus itself is no longer detectable in the circulation. An eminent immunologist once told me that the virus infection itself is removed from the blood within a day. But the presence of the virus leads to a low-level Chronic Active EBV (CAEBV) infection. [New DNA techniques make it possible to measure the viral load through EBV virus DNA in the blood of patients].
Disruption of the highly evolved balance
The herpes/EBV virus has developed a relationship with its human host that allows it to persist throughout the life of the infected individual without pathology. However, disruptions of the highly evolved balance between the virus lytic and latent cycles and host immune control result in a range of EBV-associated diseases involving B-cells, epithelial cells, T-cells, natural killer (NK) cells and muscle cells.
Loss of control of the lytic life cycle of EBV associated with CAEBV infection disrupts the virus-host balance. Here we need to differentiate between two processes, the B-lymphomas and the cell disorders as follows:
- As the virus gains access to the immune system by attaching to primary B-cells, B-cells become immortalized. In the medical literature, there is talk of severe T cell dysfunction to contain B cell replication but it might well be that a healthy immune system just produces B-cells relentlessly because they don’t work up to a point where with age there is a reduced capacity to mount an effective CD8+ T-cell response [is monoclonal gammopathy of unknown significance MGUS related?];
The interaction of the virus with infected cells causes cells to activate the NF-KB pathway and secrete cytokines and chemokines as well as inhibitory cytokines. This results in imbalances inhibitory to the activation and function of cytoxic T-lymphocytes and in an ineffective (subverted) immune response.
- Preincubation of cells with EBV also primes the cells (EBV infected polymorphonuclear leucocytes) that when stimulated start a response that leads to the release of pro-inflammatory lipid mediators (arachidonic acid or AA). In MS, the ratio Omega-3 to Omega-6 changed where ApoA1 level is reduced (25% in RR, 50% is SP and 75% in PP). This involves the fat metabolism where it is possible to get some marginal form of control over the inflammatory disease through the diet and medication (low saturated fat Swank and the anti-inflammatory properties of HDL and endothelial function; Metformin/Simvastatin reducing oxidative LDL).
A fascinating expose of the biology of EBV infection and EBV in the pathogenesis of MS including on the role of CD4+ and CD8+ T-cells and "auto"reactive B-cells (=cross reaction with transgenic cells, see next section) can be found in Pender and Burrows, Epstein-Barr virus and multiple sclerosis: potential opportunities for immunotherapy.
[As the immune system weakens with age (immunosenescence), a decline in humoral immunity/B-cells may explain the extinction of new MS cases and stabilization above the age of 60 and would also seem to confirm the involvement of the B-excessive cells in the pathogenesis of MS].
The viral tolerance theory – the typical demyelinating MS plaques explained
During periods that people are immune compromised (can be the fetal period, the period of the newborn and immune deficient periods), the virus can incorporate some of its genes in the DNA of permissible cells. As such, the virus itself is not programmed to reactivate at specific time intervals but it is the immune system that weakens.
The gene transduction occurs during immune deficiency periods. The incorporated viral genes (transgenes) are tolerant to the body or no immune memory against these transgenes has established.
In MS, in particular the oligodendrocyte precursor cells (OPCs) will be infected. These oligodendrocytic stem cells and their progenitors are preferred by the virus because they differentiate and help replicate the virus. Also for that reason the bone marrow will be infected. Chronic cerebro spinal vascular insufficiency (CCSVI or narrowed internal jugular veins) is a factor – most probably a birth defect - that broke the BBB tissue in an earlier phase. [in rheuma arthritis it is the cartilage of the joints, in MS infection of the cartilage of the sinuses is an issue that helps spreading the virus, for Crohn’s disease permissible cells are in the intestine]
People with transgenes in their body are healthy but predisposed to develop a disease. Predisposed people become diseased when they are infected with a microbe that shares epitodes with the transgenes present in the transgenic cells and will cause an immunological reaction. A chronic low-level EBV infection is suspect in MS but also a Hepatitis vaccinations has been suggested as a trigger. Crohn's disease is associated with measles.
In MS, specific T- and B-cells will pass the CNS and cross-react with the transgenes in the OPCs. Due to this cross-reaction, many OPCs will die which leads to a diminishing number of OPCs, of dendrocytes and a reduced myelination of neurons. EBV resides in the B cell and immortalizes it. So in reaction, the immune system produces more and more. [The count of EBV and herpes simplex immune cells in my circulation is very high, about 20 x max.]
During this cross-reaction, many mediators will be released by the infiltrating T-cells. This will increase angiogenesis and cause hyperproliferation of surrounding tissue cells in the CNS which in turn causes the pathological lesions (sclerotic plaques) typical for MS.
The symptoms of MS will be mild in relapse-remitting MS but severe in progressive MS depending on the kind of virus that has incorporated part of its genome in the oligodendrocytic stem cells. Inflammatory viruses such as VZV will be associated with mild diseases whereas onco viruses such as EBV will be associated with progressive MS. [I do not exclude the possibility that the VZV mechanism (microbleedings, angiopathy, acute inflammation by blocking of receptors) is followed later on by the EBV mechanism (immortalized B-cells, autoimmunity of transgenic cells) where precisely the kick-in of this latter mechanism explains the second peak in the graph of age of onset of MS. ]
The biochemical reaction hypothesis – the fatigue explained
Besides the immune reaction against the OPCs, the high load of immortalized B-cells has a second important effect. This is all about fatigue, deterioration of the cell machinery and cellular respiration, disabling glycaldehyde-3 phosphate, the peroxydisation of lipids and other disturbances crucial to the progression of MS but not necessarily major demyelination.
The immune cells have substantial super-oxygen generating capability. The superoxide reacts with the nitric oxide and forms peroxynitrite which is by far the worst free radical. Over time we produce excess peroxynitrite. Although the peroxynitrite may inhibit viral replication, it disables glyceralderhyde 3 phosphate which impacts the sodium/potassium pump and cell viability. It is a system that feeds on itself: The imbalance of the ratio of ATP to ADP to AMP causes the cell to shed AMP which further lowers ATP, the fall in adenosine lowers purine levels and uric acid falls so we lose a potent scavenger of peroxynitrite.
Over time the vitality of the cell declines as ATP levels decline and the loss of some AMP leads to a fall in Adenosine (endogenous inhibitor of arachidonic acid) and, in time, a loss of purine from Adenosine loss. Ultimately energy levels decline and uric acid levels fall. The loss of Adenosine will lower the ability to control inflammation. And the endothelium inflammates.
A cascade of events follows: further immune cells, more superoxide, more peroxynitite. These are very localised processes, short lived with restricted diffusion but still go across cell membranes. This leads to an initiation of a lipid (LDL) oxidation processes from which the lesions follow. The invasion and accumulation of white blood cells will turn the atherosclerosis/wall thickening into an endothelial dysfunction.
The huge oxidative stress jams the gates/mitochondria of the cells, causes effects on the mitochondrial electron transport chain, electron pump inactivation, inhibits ADP to ATP conversion and depletes energy in the form of ATP. And it poisons fat tissue and causes lesions where the brains, biologically seen, are just a lump of fat. I think it also causes what is called herpetic neuralgia where fibromyalgia is not far away.
The lack of energy in MS and other lesions is thus a co-morbidity factor caused by the VZV angiopathy in combination with the EBV high immune complexes. As the number of active gates goes down, we see an increasingly big temperature effect in patients with MS and a loss of muscle strength and sensitivity in the periphery which is an effect possibly as important as the disconnect in the brains. And as cells shrink in size because gates/mitochondria fail, it causes whole brain atrophy. Hence, the typical fatigue, weakening of muscles and whole-brain atrophy observed in MS patients is partly caused by the chronic VZV/EBV infection but with a completely different underlying mechanism than the demyelinating plaques in the brains.
[an extensive analysis of my blood revealed that there are only a few parameters out of their normal margin: that is the high concentration of herpes/EBV immune complexes and high titers of muscles, hence I am eating my own muscles and with that also the connection between nerves and muscles]
In parallel to the MS plaques and immune cell activation in the brain, the NF-KB is triggered by the biochemical cycle mechanism [EBV culprit?], causing elevated cytokines that contribute to raising the inflammation and Th activity. Where, at some point, mechanisms become all convolved.
A general dysregulation of the metabolism – interlocking vicious cycles
The virus is causal and leads to a general dysregulation of the metabolism.
The problem of disease progression can not be solved by metabolic factors. For sure, hormones are an influence. Hormonal deficiencies often relate to symptoms belonging to lupus, CFS or fibromyalgia or other auto immune diseases. [In my case some hormones were on the low end including cortisol and – as a derived product - testosterone]
At some point in the autoimmune disease process, the HPA axis will be affected causing hormonal deficiencies starting with cortisol. This will have its effects on the gut and further weaken the immune system, thus causing a vicious cycle. [to note: gut problems often precede an MS diagnosis; 90% of the immune system resides in the gut; the role of bacteria in the gut which may help solve autoimmune diseases such as e.g. diabetes T2, the central role of the gastro intestinal tract for good immunity]
While hormones are an influence, administration with hormones (e.g. cortical and DHEA) won’t be convincing. Without tackling the virus and the viral infection, the problem will persist.
This is also true for infection by bacteria and fungi including Borrelia and Cpn, toxoplasmose and such things as toe nail fungus [Candida infection] which get their chance when the immune system is fighting the virus [IgG3 depletion]. The infection will aggravate the situation and challenge the immune system further. It is important to get rid of all bacterial infections but fighting the infections alone won’t be enough.
Besides the endocrinological disorders and infectious diseases, there is yet another loop, from the psychological to the physiological. (Short term) stressors that initiate cases of multisystem illnesses act by stimulating nitric oxide synthase (NOS) activity and consequently produce increased levels of nitric oxide and its oxidant product peroxynitrite. Initiation is converted into a chronic illness and a lowered energy metabolism through the activation of vicious cycle mechanisms through which chronic elevation of nitric oxide and peroxynitrite is produced and maintained. All three nitric oxide synthases have been shown to be involved (eNOS, nNOS and iNOS).
The NF-KB is triggered by the biochemical cycle mechanism. The increased NF-KB activity will lead to increased iNOS activity by stimulating through the inflammatory cytokines IL's, TFN and IFN the activity of the iNOS gene itself.
There is a combination of stability and instability, positive and negative feed back loops, leading to what is essentially inflammatory biochemistry. [vicious cycle is the NO/OHNOO hypothesis – Martin Pall]
MS is therefore a subtle multi factorial disease where a number mechanisms and vicious loops are convolved. This explains the erratic course of the disease, and the large variety of symptoms and disease progression seen in MS patients.
Towards to a new paradigm for autoimmune diseases
In our current system for medicare, we see a very large number of overlapping autoimmune diseases with different names. Every expression of a neurological set of symptoms got its own name, based on several types of observations. And we see various signs and symptoms that are overlapping e.g.: slowly progressive symmetric distal sensor motor neuropathy, muscle loss, difficult urine retention, pain worse at night, gender bias, fatigue, distorted Ca levels and inactivated pump mechanisms.
But in fact, a bigger common scheme is underlying. A scheme that encompasses the wide variety of observations, their patterns of case initiation, their chronic nature and many of their shared and unique symptoms and signs of the chronic phase of the disease. A scheme that explains many unexplained observations and the multiple similarities of these illnesses by a simple conceptual framework.
We need to develop and accept a new paradigm based on the understanding of a viral cause of autoimmunity and indeed MS. Traditional major disease paradigms should be complemented by a new model based on virology and biochemistry.
Enabling the highly disruptive course
There is hardly MS among people with HIV. Patients with MS that attract HIV and start anti-HIV (= antiviral) treatment heal from MS a few years after starting with the treatment, providing an indication for the fabulous self-regenerating capacity of the human body if the causal factor is removed. Also the results of chemo therapy to kick down the virus look very promising.
I am currently studying the opportunities and possibilities for treatment of the chronically active EBV infection. This opens a whole new world in our journey of discovery. I am confident that we come ever closer to an effective treatment scheme for MS.
A new vision on autoimmunity – towards a revolution in healthcare
I am an MS patient who was trained in a technical discipline. But when I was diagnosed with MS in 2004, I became extremely motivated to unravel the disease that increasingly ruled my live and started to learn more about the disease. In the meanwhile, with my own experiences as an MS patient and the family history in mind and with the help of the vast amount of medical literature available on the Internet and some good books, some professional advice and the social and patient fora, I have become a semi-literate. The journey has led me to a new understanding of the disease that is presented here.
Paradigm changes often come unexpected and from the outside, and are motivated either by young people who are new to the field or by people who look with fresh eyes at the problem. This has definitely helped me because I did not have to unlearn, my mind was not set by old dogmatic believes that every medical student has to learn if he wants to pass his exams, and I could see new connections and concepts that others perhaps could not see, believe, accept or propose.
A critical need to open the mind set
Autoimmune diseases like Crohn’s Disease and Multiple Sclerosis (MS), in which the immune system attacks its own body rather than predatory invaders, affect 5-20% of the global community. The current scourge of immune diseases points to a growing problem of an overall weakening society. [more on scope of problem, statistics, hits ever younger people] If the trend is not changed, consequences for the general health of our population and that of future generations may be far reaching.
We must spot current trends in societal health, take these trends extremely serious and investigate what is driving them as a matter of urgency. To this end, we should question the status-quo on autoimmunity.
However, as the weight of the status-quo is so immense, every change proposal is at risk to collapse under that weight. Significant systemic problems are pervasive and hamper a course towards investigating or even considering alternative views. The risk is a stagnation while the debate does not get a fair chance and may be dead even before it has started.
In order to find a way out of the impasse, it will be critically necessary that the matter is approached with an open mind, and that alternative views on autoimmunity are explored and new connections investigated with urgency and with force.
The viral connection
The current scourge of immune disease is explained by an immune system that gets ever weaker. There is a multitude of underlying factors: an unhealthy diet (the ratio of Omega 3 to Omega 6 and satured fats drastically changed from 1:1 to 1:16, we forgot about fish on Fridays, the balance of fatty acid intake is important for homeostasis and normal development, the emergence of inflammatory diseases correlates to the evolutionary aspects of our diet), poor quality food (e.g. engrainisation, ‘hardened’ wheat, soil depletion, a lack of flavonoids which generate antioxidants, lack of earthing, hydroponic plant growth), a lack of immune system training (e.g. extreme hygiene and indoor/office life, we forgot about fasting which is deep in the Old Testament and, people who work outdoors are generally much healthier - earthing), and stress in a very broad sense.
When the immune system weakens, the herpes virus can surface [herpes is a family of viruses]. Most of the human population have it and it has been with us for millions of years, even when we were still apes hanging in the trees of Africa. But all the time it was kept in control by a good functioning immune system. However, the last 50 years, something new is happening that has not been seen before in the history of mankind [on a smaller scale: Sumeria (overfarming) and the black death (people in the upper class of society were more immune because of diet) and more recently the outbreak of diseases like the swine flu].
Our living conditions have changed so profoundly that the immune system does not keep the virus in check anymore.
The virus – host balance
The primate immune system and the herpes virus have coevolved alongside, for million of years. The fact that cytomegalovirus-like viruses are found in very many species – including in fish - suggests that it evolved along side with us even longer and adjusted itself entirely on man. In fact, humans and the virus keep each other in balance where the virus helped along the long, joint road through attack and defense to build up our present immune system.
The virus nests in the cells, and occasional breaks out and causes major changes in the immune system by the formation of highly aggressive effector T-cells (CD4 + and CD8 +). This type of immune cells for their survival depends on the presence of the herpes virus and comes in healthy people only when they are infected with the virus which itself is no longer detectable.
The relationship between the well detectable CD4 + and the CD8 + T cells and the virus means that the virus itself is somewhere in the body tucked deep inside the endothelium. The virus itself is no longer detectable in the circulation. An eminent immunologist once told me that the virus infection itself is removed from the blood within a day. But the presence of the virus leads to a low-level Chronic Active EBV (CAEBV) infection. [New DNA techniques make it possible to measure the viral load through EBV virus DNA in the blood of patients].
Disruption of the highly evolved balance
The herpes/EBV virus has developed a relationship with its human host that allows it to persist throughout the life of the infected individual without pathology. However, disruptions of the highly evolved balance between the virus lytic and latent cycles and host immune control result in a range of EBV-associated diseases involving B-cells, epithelial cells, T-cells, natural killer (NK) cells and muscle cells.
Loss of control of the lytic life cycle of EBV associated with CAEBV infection disrupts the virus-host balance. Here we need to differentiate between two processes, the B-lymphomas and the cell disorders as follows:
- As the virus gains access to the immune system by attaching to primary B-cells, B-cells become immortalized. In the medical literature, there is talk of severe T cell dysfunction to contain B cell replication but it might well be that a healthy immune system just produces B-cells relentlessly because they don’t work up to a point where with age there is a reduced capacity to mount an effective CD8+ T-cell response [is monoclonal gammopathy of unknown significance MGUS related?];
The interaction of the virus with infected cells causes cells to activate the NF-KB pathway and secrete cytokines and chemokines as well as inhibitory cytokines. This results in imbalances inhibitory to the activation and function of cytoxic T-lymphocytes and in an ineffective (subverted) immune response.
- Preincubation of cells with EBV also primes the cells (EBV infected polymorphonuclear leucocytes) that when stimulated start a response that leads to the release of pro-inflammatory lipid mediators (arachidonic acid or AA). In MS, the ratio Omega-3 to Omega-6 changed where ApoA1 level is reduced (25% in RR, 50% is SP and 75% in PP). This involves the fat metabolism where it is possible to get some marginal form of control over the inflammatory disease through the diet and medication (low saturated fat Swank and the anti-inflammatory properties of HDL and endothelial function; Metformin/Simvastatin reducing oxidative LDL).
A fascinating expose of the biology of EBV infection and EBV in the pathogenesis of MS including on the role of CD4+ and CD8+ T-cells and "auto"reactive B-cells (=cross reaction with transgenic cells, see next section) can be found in Pender and Burrows, Epstein-Barr virus and multiple sclerosis: potential opportunities for immunotherapy.
[As the immune system weakens with age (immunosenescence), a decline in humoral immunity/B-cells may explain the extinction of new MS cases and stabilization above the age of 60 and would also seem to confirm the involvement of the B-excessive cells in the pathogenesis of MS].
The viral tolerance theory – the typical demyelinating MS plaques explained
During periods that people are immune compromised (can be the fetal period, the period of the newborn and immune deficient periods), the virus can incorporate some of its genes in the DNA of permissible cells. As such, the virus itself is not programmed to reactivate at specific time intervals but it is the immune system that weakens.
The gene transduction occurs during immune deficiency periods. The incorporated viral genes (transgenes) are tolerant to the body or no immune memory against these transgenes has established.
In MS, in particular the oligodendrocyte precursor cells (OPCs) will be infected. These oligodendrocytic stem cells and their progenitors are preferred by the virus because they differentiate and help replicate the virus. Also for that reason the bone marrow will be infected. Chronic cerebro spinal vascular insufficiency (CCSVI or narrowed internal jugular veins) is a factor – most probably a birth defect - that broke the BBB tissue in an earlier phase. [in rheuma arthritis it is the cartilage of the joints, in MS infection of the cartilage of the sinuses is an issue that helps spreading the virus, for Crohn’s disease permissible cells are in the intestine]
People with transgenes in their body are healthy but predisposed to develop a disease. Predisposed people become diseased when they are infected with a microbe that shares epitodes with the transgenes present in the transgenic cells and will cause an immunological reaction. A chronic low-level EBV infection is suspect in MS but also a Hepatitis vaccinations has been suggested as a trigger. Crohn's disease is associated with measles.
In MS, specific T- and B-cells will pass the CNS and cross-react with the transgenes in the OPCs. Due to this cross-reaction, many OPCs will die which leads to a diminishing number of OPCs, of dendrocytes and a reduced myelination of neurons. EBV resides in the B cell and immortalizes it. So in reaction, the immune system produces more and more. [The count of EBV and herpes simplex immune cells in my circulation is very high, about 20 x max.]
During this cross-reaction, many mediators will be released by the infiltrating T-cells. This will increase angiogenesis and cause hyperproliferation of surrounding tissue cells in the CNS which in turn causes the pathological lesions (sclerotic plaques) typical for MS.
The symptoms of MS will be mild in relapse-remitting MS but severe in progressive MS depending on the kind of virus that has incorporated part of its genome in the oligodendrocytic stem cells. Inflammatory viruses such as VZV will be associated with mild diseases whereas onco viruses such as EBV will be associated with progressive MS. [I do not exclude the possibility that the VZV mechanism (microbleedings, angiopathy, acute inflammation by blocking of receptors) is followed later on by the EBV mechanism (immortalized B-cells, autoimmunity of transgenic cells) where precisely the kick-in of this latter mechanism explains the second peak in the graph of age of onset of MS. ]
The biochemical reaction hypothesis – the fatigue explained
Besides the immune reaction against the OPCs, the high load of immortalized B-cells has a second important effect. This is all about fatigue, deterioration of the cell machinery and cellular respiration, disabling glycaldehyde-3 phosphate, the peroxydisation of lipids and other disturbances crucial to the progression of MS but not necessarily major demyelination.
The immune cells have substantial super-oxygen generating capability. The superoxide reacts with the nitric oxide and forms peroxynitrite which is by far the worst free radical. Over time we produce excess peroxynitrite. Although the peroxynitrite may inhibit viral replication, it disables glyceralderhyde 3 phosphate which impacts the sodium/potassium pump and cell viability. It is a system that feeds on itself: The imbalance of the ratio of ATP to ADP to AMP causes the cell to shed AMP which further lowers ATP, the fall in adenosine lowers purine levels and uric acid falls so we lose a potent scavenger of peroxynitrite.
Over time the vitality of the cell declines as ATP levels decline and the loss of some AMP leads to a fall in Adenosine (endogenous inhibitor of arachidonic acid) and, in time, a loss of purine from Adenosine loss. Ultimately energy levels decline and uric acid levels fall. The loss of Adenosine will lower the ability to control inflammation. And the endothelium inflammates.
A cascade of events follows: further immune cells, more superoxide, more peroxynitite. These are very localised processes, short lived with restricted diffusion but still go across cell membranes. This leads to an initiation of a lipid (LDL) oxidation processes from which the lesions follow. The invasion and accumulation of white blood cells will turn the atherosclerosis/wall thickening into an endothelial dysfunction.
The huge oxidative stress jams the gates/mitochondria of the cells, causes effects on the mitochondrial electron transport chain, electron pump inactivation, inhibits ADP to ATP conversion and depletes energy in the form of ATP. And it poisons fat tissue and causes lesions where the brains, biologically seen, are just a lump of fat. I think it also causes what is called herpetic neuralgia where fibromyalgia is not far away.
The lack of energy in MS and other lesions is thus a co-morbidity factor caused by the VZV angiopathy in combination with the EBV high immune complexes. As the number of active gates goes down, we see an increasingly big temperature effect in patients with MS and a loss of muscle strength and sensitivity in the periphery which is an effect possibly as important as the disconnect in the brains. And as cells shrink in size because gates/mitochondria fail, it causes whole brain atrophy. Hence, the typical fatigue, weakening of muscles and whole-brain atrophy observed in MS patients is partly caused by the chronic VZV/EBV infection but with a completely different underlying mechanism than the demyelinating plaques in the brains.
[an extensive analysis of my blood revealed that there are only a few parameters out of their normal margin: that is the high concentration of herpes/EBV immune complexes and high titers of muscles, hence I am eating my own muscles and with that also the connection between nerves and muscles]
In parallel to the MS plaques and immune cell activation in the brain, the NF-KB is triggered by the biochemical cycle mechanism [EBV culprit?], causing elevated cytokines that contribute to raising the inflammation and Th activity. Where, at some point, mechanisms become all convolved.
A general dysregulation of the metabolism – interlocking vicious cycles
The virus is causal and leads to a general dysregulation of the metabolism.
The problem of disease progression can not be solved by metabolic factors. For sure, hormones are an influence. Hormonal deficiencies often relate to symptoms belonging to lupus, CFS or fibromyalgia or other auto immune diseases. [In my case some hormones were on the low end including cortisol and – as a derived product - testosterone]
At some point in the autoimmune disease process, the HPA axis will be affected causing hormonal deficiencies starting with cortisol. This will have its effects on the gut and further weaken the immune system, thus causing a vicious cycle. [to note: gut problems often precede an MS diagnosis; 90% of the immune system resides in the gut; the role of bacteria in the gut which may help solve autoimmune diseases such as e.g. diabetes T2, the central role of the gastro intestinal tract for good immunity]
While hormones are an influence, administration with hormones (e.g. cortical and DHEA) won’t be convincing. Without tackling the virus and the viral infection, the problem will persist.
This is also true for infection by bacteria and fungi including Borrelia and Cpn, toxoplasmose and such things as toe nail fungus [Candida infection] which get their chance when the immune system is fighting the virus [IgG3 depletion]. The infection will aggravate the situation and challenge the immune system further. It is important to get rid of all bacterial infections but fighting the infections alone won’t be enough.
Besides the endocrinological disorders and infectious diseases, there is yet another loop, from the psychological to the physiological. (Short term) stressors that initiate cases of multisystem illnesses act by stimulating nitric oxide synthase (NOS) activity and consequently produce increased levels of nitric oxide and its oxidant product peroxynitrite. Initiation is converted into a chronic illness and a lowered energy metabolism through the activation of vicious cycle mechanisms through which chronic elevation of nitric oxide and peroxynitrite is produced and maintained. All three nitric oxide synthases have been shown to be involved (eNOS, nNOS and iNOS).
The NF-KB is triggered by the biochemical cycle mechanism. The increased NF-KB activity will lead to increased iNOS activity by stimulating through the inflammatory cytokines IL's, TFN and IFN the activity of the iNOS gene itself.
There is a combination of stability and instability, positive and negative feed back loops, leading to what is essentially inflammatory biochemistry. [vicious cycle is the NO/OHNOO hypothesis – Martin Pall]
MS is therefore a subtle multi factorial disease where a number mechanisms and vicious loops are convolved. This explains the erratic course of the disease, and the large variety of symptoms and disease progression seen in MS patients.
Towards to a new paradigm for autoimmune diseases
In our current system for medicare, we see a very large number of overlapping autoimmune diseases with different names. Every expression of a neurological set of symptoms got its own name, based on several types of observations. And we see various signs and symptoms that are overlapping e.g.: slowly progressive symmetric distal sensor motor neuropathy, muscle loss, difficult urine retention, pain worse at night, gender bias, fatigue, distorted Ca levels and inactivated pump mechanisms.
But in fact, a bigger common scheme is underlying. A scheme that encompasses the wide variety of observations, their patterns of case initiation, their chronic nature and many of their shared and unique symptoms and signs of the chronic phase of the disease. A scheme that explains many unexplained observations and the multiple similarities of these illnesses by a simple conceptual framework.
We need to develop and accept a new paradigm based on the understanding of a viral cause of autoimmunity and indeed MS. Traditional major disease paradigms should be complemented by a new model based on virology and biochemistry.
Enabling the highly disruptive course
There is hardly MS among people with HIV. Patients with MS that attract HIV and start anti-HIV (= antiviral) treatment heal from MS a few years after starting with the treatment, providing an indication for the fabulous self-regenerating capacity of the human body if the causal factor is removed. Also the results of chemo therapy to kick down the virus look very promising.
I am currently studying the opportunities and possibilities for treatment of the chronically active EBV infection. This opens a whole new world in our journey of discovery. I am confident that we come ever closer to an effective treatment scheme for MS.
Last edited by Leonard on Tue Feb 10, 2015 5:25 am, edited 5 times in total.
Re: A new concept and treatment options for MS
Hi Leo,
Your last few posts are really interesting. Sorry I haven't replied earlier. I will have to think about them for a while. The observation of the decline in humoral immunity of B cells as we age is something I haven't looked at but that mechanism deserves exploration as it may explain why EBV infection affects us differently than the broader population. We all should have a good look at this.
On your overheating at night issue; it's a tricky one to solve unless you live in an house by yourself. I had similar thoughts about it a while ago and found trying to improve vasodilation by using L-arginine helped. Sinatra's use of Carnitine in conjunction with Q10 is something I've adopted and I find that has helped my responses to heat normalize. I have also added N-acetyl-cysteine so I should mention that as well. We have just passed through the heat of summer down here and I managed very well. Ducted heating is a different heat. Don't forget you will be throwing potential allergens out of the ducts when you use it. Maybe you could try using those radiant heat oil heaters to warm the air rather than blow stuff into the air. It might be a subtle difference that just works. We don't get as cold as the Northern hemisphere so forgive me if that's impractical.
Regards
Your last few posts are really interesting. Sorry I haven't replied earlier. I will have to think about them for a while. The observation of the decline in humoral immunity of B cells as we age is something I haven't looked at but that mechanism deserves exploration as it may explain why EBV infection affects us differently than the broader population. We all should have a good look at this.
On your overheating at night issue; it's a tricky one to solve unless you live in an house by yourself. I had similar thoughts about it a while ago and found trying to improve vasodilation by using L-arginine helped. Sinatra's use of Carnitine in conjunction with Q10 is something I've adopted and I find that has helped my responses to heat normalize. I have also added N-acetyl-cysteine so I should mention that as well. We have just passed through the heat of summer down here and I managed very well. Ducted heating is a different heat. Don't forget you will be throwing potential allergens out of the ducts when you use it. Maybe you could try using those radiant heat oil heaters to warm the air rather than blow stuff into the air. It might be a subtle difference that just works. We don't get as cold as the Northern hemisphere so forgive me if that's impractical.
Regards
Re: A new concept and treatment options for MS
Since you guys are interested in anti-viral therapy for herpes, consider this entry by flora68 dating Nov 1, 2006 (updated in 2011). It would be nice to know how she is doing now.
"I just wanted to pop in and let you guys know how I'm doing and what's been added to my anti-MS regimen, FYI.
Basically I'm doing great! I really don't feel the MS at all. I still can't take excess heat and I doubt that that'll change, so hiding from the Texas heat all summer is tedious and sometimes isolating, but totally do-able. (Today in Austin it really feels like autumn, and I'm pumped!)
I did have a definite setback, but it occurred during the only time I was off LDN (I briefly ran out), and it gave me a whole new, totally miserable symptom (more about that below), and believe me, I will NEVER run out of LDN again!
To backtrack, I started on LDN (3mg) on February 10th, 2005. Within weeks I felt like a whole new person, and that's still the case.
But due to a faxing error between the out-of-town pharmacy and my doctor's office, I was off LDN for about a week in April, 2005, resulting in severe pain, no energy, and the beginnings of serious inner ear problems. I finally received and started taking the LDN again and awakened the next morning feeling WONDERFUL in terms of pain and energy!
But the inner ear symptoms escalated sharply anyway, to the point that I had a constant feeling of motion sickness, not only if I moved, but even if I just saw something move, or even if just my eyeballs moved at all! Have you ever had to literally hold your eyeballs still with your fingers (through the eyelids)?
I have, for days on end, and it really, really sucks to be that sick. I can take a lot of pain but nausea really undoes me.
Anyway, it turned out to be a severe case of viral labyrinthitis, and after a week of it I was so dehydrated from the constant vomitting that I wound up in the ER at the end of April '05 for IV fluids and K+.
But the upside of all that misery was that I was sent to a brilliant, innovative oto-(inner-ear)neurologist who happens to be VERY pro-LDN. In fact, I got the impression that ALL of his MS patients are on LDN.
He did a ton of complicated tests on my brain, balance, hearing, cognitive functions, etc., and told me that my labyrinthitis as just another part of MS for me.
Like many researchers, he believes that MS is (partly) triggered by a herpes virus (nothing new there, lots of people believe that), the same virus that is almost always responsible for viral labyrinthitis.
He believes in treating the virus primarily, which he says also treats the MS primarily, which is something that neither the CRABs nor Tysabri claim to do. But it's a long term thing; it's especially hard to stop a virus (or any infection) that's deep in your head.
So I'm still on LDN and probably always will be, but we upped the dose to 4.5 mg. And the doc gradually eased me into anti-viral treatment.
(Gradually because he said that suddenly starting on a strong anti-viral can actually trigger the MS to flair up in some people.)
So first he put me on Lauricidin, a natural lipid that has shown antibacterial, antifungal, anti-yeast and antiviral properties. Here's their website: http://www.lauricidin.com/default.asp
After 6 weeks on Lauricidin (with no side effects at all), I was switched to a very small dose of Valtrex (125 mg twice a day). As a matter of fact, that was a year ago yesterday, last Halloween ('05) ...(boo! )
After a couple of months on Valtrex the dosage was doubled to 500mg total daily, split into two 250mg doses), also with absolutely NO side effects. (None are expected with this cautious protocal). I'm still on that dosage.
My follow-up assessments started getting better and better, and my labyrinthitis symptoms are almost totally gone. Last month the doc added amantadine as well, another anti-viral that helps many people with the viral aspects of MS, and it'll also likely prevent the flu as long as I'm on it. But the amantadine is just for a couple of months.
This doc is big on testing and fine-tuning various hormone levels as well as testing for heavy metals. He feels that getting all that stuff in balance is critical. He's into naturopathic and conventional medicine, open to whatever really works. And he's into the science of it, not subjective or anecdotal assessments.
So, I'm feeling great, and MS really isn't an issue at all for me now that the weather's cooled off again (last fall and winter were great for me too), and the Texas Longhorns are having another brilliant season, so life is good.
The only drawback now to my MS diagnosis is that my insurance premiums doubled , twice in the last two years, to over $900 a month, so I've finally had to drop it. In fact, today is my first day totally uninsured, so wish me luck on that! Fortunately LDN is literally cheaper than water around here, but the insurance never would have covered it anyway.
Lastly, let me say that I do realize that LDN hasn't worked for everybody, and I'm sorry if my enthusiastic posts irritate people who had bad luck with it. But I can't help but feel that it's still worth a try. In fact, I really think that MS patients should try LDN first, not as a last resort; it's been two years and I still have countless lumps and dents from Copaxone injections. Not to mention spectacular debt! What a waste!
Hope you're doing well out there. I guess a lot of people are on Tysabri now, huh? Well, whatever floats your boat...
Good luck to us all.
flora "
"I just wanted to pop in and let you guys know how I'm doing and what's been added to my anti-MS regimen, FYI.
Basically I'm doing great! I really don't feel the MS at all. I still can't take excess heat and I doubt that that'll change, so hiding from the Texas heat all summer is tedious and sometimes isolating, but totally do-able. (Today in Austin it really feels like autumn, and I'm pumped!)
I did have a definite setback, but it occurred during the only time I was off LDN (I briefly ran out), and it gave me a whole new, totally miserable symptom (more about that below), and believe me, I will NEVER run out of LDN again!
To backtrack, I started on LDN (3mg) on February 10th, 2005. Within weeks I felt like a whole new person, and that's still the case.
But due to a faxing error between the out-of-town pharmacy and my doctor's office, I was off LDN for about a week in April, 2005, resulting in severe pain, no energy, and the beginnings of serious inner ear problems. I finally received and started taking the LDN again and awakened the next morning feeling WONDERFUL in terms of pain and energy!
But the inner ear symptoms escalated sharply anyway, to the point that I had a constant feeling of motion sickness, not only if I moved, but even if I just saw something move, or even if just my eyeballs moved at all! Have you ever had to literally hold your eyeballs still with your fingers (through the eyelids)?
I have, for days on end, and it really, really sucks to be that sick. I can take a lot of pain but nausea really undoes me. Anyway, it turned out to be a severe case of viral labyrinthitis, and after a week of it I was so dehydrated from the constant vomitting that I wound up in the ER at the end of April '05 for IV fluids and K+.
But the upside of all that misery was that I was sent to a brilliant, innovative oto-(inner-ear)neurologist who happens to be VERY pro-LDN. In fact, I got the impression that ALL of his MS patients are on LDN.
He did a ton of complicated tests on my brain, balance, hearing, cognitive functions, etc., and told me that my labyrinthitis as just another part of MS for me.
Like many researchers, he believes that MS is (partly) triggered by a herpes virus (nothing new there, lots of people believe that), the same virus that is almost always responsible for viral labyrinthitis.
He believes in treating the virus primarily, which he says also treats the MS primarily, which is something that neither the CRABs nor Tysabri claim to do. But it's a long term thing; it's especially hard to stop a virus (or any infection) that's deep in your head.
So I'm still on LDN and probably always will be, but we upped the dose to 4.5 mg. And the doc gradually eased me into anti-viral treatment.
(Gradually because he said that suddenly starting on a strong anti-viral can actually trigger the MS to flair up in some people.)
So first he put me on Lauricidin, a natural lipid that has shown antibacterial, antifungal, anti-yeast and antiviral properties. Here's their website: http://www.lauricidin.com/default.asp
After 6 weeks on Lauricidin (with no side effects at all), I was switched to a very small dose of Valtrex (125 mg twice a day). As a matter of fact, that was a year ago yesterday, last Halloween ('05) ...(boo! )
After a couple of months on Valtrex the dosage was doubled to 500mg total daily, split into two 250mg doses), also with absolutely NO side effects. (None are expected with this cautious protocal). I'm still on that dosage.
My follow-up assessments started getting better and better, and my labyrinthitis symptoms are almost totally gone. Last month the doc added amantadine as well, another anti-viral that helps many people with the viral aspects of MS, and it'll also likely prevent the flu as long as I'm on it. But the amantadine is just for a couple of months.
This doc is big on testing and fine-tuning various hormone levels as well as testing for heavy metals. He feels that getting all that stuff in balance is critical. He's into naturopathic and conventional medicine, open to whatever really works. And he's into the science of it, not subjective or anecdotal assessments.
So, I'm feeling great, and MS really isn't an issue at all for me now that the weather's cooled off again (last fall and winter were great for me too), and the Texas Longhorns are having another brilliant season, so life is good. The only drawback now to my MS diagnosis is that my insurance premiums doubled , twice in the last two years, to over $900 a month, so I've finally had to drop it. In fact, today is my first day totally uninsured, so wish me luck on that! Fortunately LDN is literally cheaper than water around here, but the insurance never would have covered it anyway.
Lastly, let me say that I do realize that LDN hasn't worked for everybody, and I'm sorry if my enthusiastic posts irritate people who had bad luck with it. But I can't help but feel that it's still worth a try. In fact, I really think that MS patients should try LDN first, not as a last resort; it's been two years and I still have countless lumps and dents from Copaxone injections. Not to mention spectacular debt! What a waste!
Hope you're doing well out there. I guess a lot of people are on Tysabri now, huh? Well, whatever floats your boat...
Good luck to us all.
flora "
Re: A new concept and treatment options for MS
The impression I got was the LDN was a pain receptor modulator with conflicting reports that it modulates inflammation so an update would be interesting. The use of antivirals in conjunction may be helpful. I don't know how it impacts on a users general well being. Never say never but an update would help.
Regards
Regards
Re: A new concept and treatment options for MS
In studying prospects for EBV treatment, the latent and lytic infection, tissue infection vs EBV-infected B-lymphocytes, the various ways to treat, the various working mechanisms of antivirals, the overlap of MS with other diseases such as MGUS, peripheral neuropathy, fybromyalgia, Myalgic Encephalomyelitis, CFS (where a common factor mentioned is EBV!, the common cause? see e.g. http://nl.wikipedia.org/wiki/Myalgische ... lomyelitis ), etc, I bumped into this paper: Cordycepin is a novel chemical suppressor of Epstein-Barr virus replication
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4303894/
Cordycepin is an adenosine derivative; cordycepin treatment significantly downregulated most EBV genes tested.
It struck me that this apparently relates to the vitality of the cells in our earlier work. I quote from the thesis above (which were really Scott's words): Over time the vitality of the cell declines as ATP levels decline and the loss of some AMP leads to a fall in adenosine (an endogeneous inhibitor of arachidonic acid) ... unquote.
So wat is happening here? Could it be that the detoriation of the cell machinery (peroxynitrite, ccsvi hypoperfusion) causes a fall in adenosine where the loss of adenosine lowers the ability to control inflammation and then EBV gets its way? Or lowers the ability to control inflammation precisely because EBV gets its way? Where the arachidonic acid issue is just a side issue? Not impossible..
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4303894/
Cordycepin is an adenosine derivative; cordycepin treatment significantly downregulated most EBV genes tested.
It struck me that this apparently relates to the vitality of the cells in our earlier work. I quote from the thesis above (which were really Scott's words): Over time the vitality of the cell declines as ATP levels decline and the loss of some AMP leads to a fall in adenosine (an endogeneous inhibitor of arachidonic acid) ... unquote.
So wat is happening here? Could it be that the detoriation of the cell machinery (peroxynitrite, ccsvi hypoperfusion) causes a fall in adenosine where the loss of adenosine lowers the ability to control inflammation and then EBV gets its way? Or lowers the ability to control inflammation precisely because EBV gets its way? Where the arachidonic acid issue is just a side issue? Not impossible..
Last edited by Leonard on Mon Feb 16, 2015 1:21 am, edited 2 times in total.
Re: A new concept and treatment options for MS
Hi Leo,
You're writing some great stuff at the moment. I wish I had a little more time to follow up.
On the humoural immunity note this might help. There is a diagram on the left that shows how it works. I also note further down my old friend peptidoglycan gets a mention. You're definitely on the right track.
On cordycepin, which is derived from cordyceps, it's worth noting that Gilenya is a derivative. I tried Cordyceps Sinesis which Buhner recommends but it was too harsh on my stomach. It doesn't have the same side effects as Gilenya (JCV)either.
I noticed when I looked up Cordycepin that it has adenosine and ribose. Both these occur in the ATP and so perhaps it helps strengthen that as well.
When I get some time I will go through your recent work in detail.
Regards,
You're writing some great stuff at the moment. I wish I had a little more time to follow up.
On the humoural immunity note this might help. There is a diagram on the left that shows how it works. I also note further down my old friend peptidoglycan gets a mention. You're definitely on the right track.
On cordycepin, which is derived from cordyceps, it's worth noting that Gilenya is a derivative. I tried Cordyceps Sinesis which Buhner recommends but it was too harsh on my stomach. It doesn't have the same side effects as Gilenya (JCV)either.
I noticed when I looked up Cordycepin that it has adenosine and ribose. Both these occur in the ATP and so perhaps it helps strengthen that as well.
When I get some time I will go through your recent work in detail.
Regards,
Re: A new concept and treatment options for MS
Hi Scott,
It is interesting that you note that Gilenya (fingolomid) is a derivative of cordycepin.
With the knowledge that cordycepin is a novel chemical suppressor of EBV replication (see article below), it would seem that the mechanism of action of fingolomid as described in the EMA note (second link below) is all guess work… Where the broader concept has not been seen or fully understood.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4303894/
http://www.ema.europa.eu/ema/index.jsp? ... 058001d125
With the viral connection of autoimmunity, I wonder what else in this medicine world is guess work. I think with the new insight that EBV lies at the origin of autoimmunity and probably several cancers like (non)Hodgkin, many of these medicine flyers and public assessment reports will have to be revisited.
By that same token, I wonder whether the mechanisms of action of the chemo therapy for (non)Hodgkin have been suffiently understood. Perhaps, if the EBV virus is causal for the Hodgkin, the chemo also tackles the virus. The next obvious question then is: should all MS patients seek (non)Hodgkin chemo to knock down the virus?
I am dead serious. And in certain a way, we are still better off than those with (non)Hodgkin. But if it would help to recover from progressive MS with even a glimpse of hope for a better future, I would know what to do.
Regards, Leo
It is interesting that you note that Gilenya (fingolomid) is a derivative of cordycepin.
With the knowledge that cordycepin is a novel chemical suppressor of EBV replication (see article below), it would seem that the mechanism of action of fingolomid as described in the EMA note (second link below) is all guess work… Where the broader concept has not been seen or fully understood.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4303894/
http://www.ema.europa.eu/ema/index.jsp? ... 058001d125
With the viral connection of autoimmunity, I wonder what else in this medicine world is guess work. I think with the new insight that EBV lies at the origin of autoimmunity and probably several cancers like (non)Hodgkin, many of these medicine flyers and public assessment reports will have to be revisited.
By that same token, I wonder whether the mechanisms of action of the chemo therapy for (non)Hodgkin have been suffiently understood. Perhaps, if the EBV virus is causal for the Hodgkin, the chemo also tackles the virus. The next obvious question then is: should all MS patients seek (non)Hodgkin chemo to knock down the virus?
I am dead serious. And in certain a way, we are still better off than those with (non)Hodgkin. But if it would help to recover from progressive MS with even a glimpse of hope for a better future, I would know what to do.
Regards, Leo
Re: A new concept and treatment options for MS
This paper from 2012 goes into that same direction:
Ghent researchers discover how virus switches off the immune system
21 AUGUST 2012 | IDR
Ghent scientists, along with German and French colleagues discovered how the Epstein-Barr virus (EBV) switches off our immune system. For this, they made use of accurate 3D images. Then you can see how EBV breaks down human cytokine protein. Cytokine creates immune defenses. "Our body can no longer detect viruses and kill them," say the researchers. EBV is the basis of multiple sclerosis, chronic fatigue syndrome (CFS), mononucleosis and some cancers. The discovery is a first step to a means to stop the virus.
http://www.standaard.be/cnt/dmf20120820_00264662
other press clippings on this study:
http://www.hln.be/hln/nl/961/Wetenschap ... eeld.dhtml
http://www.nieuwsblad.be/cnt/dmf20120820_117
Ghent researchers discover how virus switches off the immune system
21 AUGUST 2012 | IDR
Ghent scientists, along with German and French colleagues discovered how the Epstein-Barr virus (EBV) switches off our immune system. For this, they made use of accurate 3D images. Then you can see how EBV breaks down human cytokine protein. Cytokine creates immune defenses. "Our body can no longer detect viruses and kill them," say the researchers. EBV is the basis of multiple sclerosis, chronic fatigue syndrome (CFS), mononucleosis and some cancers. The discovery is a first step to a means to stop the virus.
http://www.standaard.be/cnt/dmf20120820_00264662
other press clippings on this study:
http://www.hln.be/hln/nl/961/Wetenschap ... eeld.dhtml
http://www.nieuwsblad.be/cnt/dmf20120820_117
Last edited by Leonard on Mon Feb 23, 2015 2:54 am, edited 1 time in total.
Re: A new concept and treatment options for MS
This brings MS and lymphoma together: http://en.wikipedia.org/wiki/Alemtuzumab
It is a monoclonal antibody.
In the Netherlands, there is apparently a trial running with Lemtrada for MS.
We can see three main avenues for treatment of the Chronic Active EBV:
- monoclonal antibodies
- anti viral medication
- anti viral T-cell therapy
It is a monoclonal antibody.
In the Netherlands, there is apparently a trial running with Lemtrada for MS.
We can see three main avenues for treatment of the Chronic Active EBV:
- monoclonal antibodies
- anti viral medication
- anti viral T-cell therapy
Last edited by Leonard on Sat Feb 21, 2015 12:33 am, edited 1 time in total.
Re: A new concept and treatment options for MS
Hi Leo,
Do you have access to the original article about EBV mentioned in that newspaper? I'm afraid my German is nonexistent so I can't really follow it.
Regards
Do you have access to the original article about EBV mentioned in that newspaper? I'm afraid my German is nonexistent so I can't really follow it.
Regards
Re: A new concept and treatment options for MS
You can try the google translator. https://translate.google.com/ It may not be perfect, but you'll likely be able to read it.Scott1 wrote:Do you have access to the original article about EBV mentioned in that newspaper? I'm afraid my German is nonexistent so I can't really follow it.