Scientists Discover Robust Evidence That Chronic Fatigue Syndrome Is a Biological Illness

For those who missed Mady Hornig's talk at the P2P Workshop, the press release below announces the research she discussed. 

Essentially, what the researchers found was an upregulated immune response in ME/CFS patients ill for three years or less, followed by "immune exhaustion." (You can read a summary of her talk HERE. It's half way down the page.)

This research supports Dr. Cheney's early hypothesis that an infectious agent causes increased cytokine production (he focused on interferon alpha), which in turn led to excitotoxicity in the brain. It also supports Dr. Bell's one-two punch theory, in which an original insult sets the stage for immune dysregulation and chronicity.

The Columbia findings not only help establish a natural history of the disease, they also support the theory that the driving mechanism for the illness is CNS inflammation. When cytokines are released in the brain, due to injury or infection, they stimulate microglial activation, which in turn produces inflammation. The recent PET scan study by Nakatomi et al. which found neuroinflammation in the brains of ME/CFS patients due to microglial activation dovetails neatly with the Columbia study. Previous studies conducted by Stanford and other researchers which have found brain abnormalities, implicate CNS inflammation as the underlying driver of symptomatology as well.

You can read the full text of the Columbia study HERE.
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Immune Signatures in Blood Point to Distinct Disease Stages, Open Door to Better Diagnosis and Treatment

NEW YORK (Feb. 27, 2015)—Researchers at the Center for Infection and Immunity at Columbia University’s Mailman School of Public Health identified distinct immune changes in patients diagnosed with chronic fatigue syndrome, known medically as myalgic encephalomyelitis (ME/CFS) or systemic exertion intolerance disease. The findings could help improve diagnosis and identify treatment options for the disabling disorder, in which symptoms range from extreme fatigue and difficulty concentrating to headaches and muscle pain.

These immune signatures represent the first robust physical evidence that ME/CFS is a biological illness as opposed to a psychological disorder, and the first evidence that the disease has distinct stages. Results appear online in the new American Association for the Advancement of Science journal, Science Advances.

With funding to support studies of immune and infectious mechanisms of disease from the Chronic Fatigue Initiative of the Hutchins Family Foundation, the researchers used immunoassay testing methods to determine the levels of 51 immune biomarkers in blood plasma samples collected through two multicenter studies that represented a total of 298 ME/CFS patients and 348 healthy controls. They found specific patterns in patients who had the disease three years or less that were not present in controls or in patients who had the disease for more than three years. Short duration patients had increased amounts of many different types of immune molecules called cytokines. The association was unusually strong with a cytokine called interferon gamma that has been linked to the fatigue that follows many viral infections, including Epstein-Barr virus (the cause of infectious mononucleosis). Cytokine levels were not explained by symptom severity.

“We now have evidence confirming what millions of people with this disease already know, that ME/CFS isn't psychological,” states lead author Mady Hornig, MD, director of translational research at the Center for Infection and Immunity and associate professor of Epidemiology at Columbia’s Mailman School. “Our results should accelerate the process of establishing the diagnosis after individuals first fall ill as well as discovery of new treatment strategies focusing on these early blood markers.”

There are already human monoclonal antibodies on the market that can dampen levels of a cytokine called interleukin-17A that is among those the study shows were elevated in early-stage patients. Before any drugs can be tested in a clinical trial, Dr. Hornig and colleagues hope to replicate the current, cross-sectional results in a longitudinal study that follows patients for a year to see how cytokine levels, including interleukin-17A, differ within individual patients over time, depending on how long they have had the disease.

Stuck in High Gear

The study supports the idea that ME/CFS may reflect an infectious “hit-and-run” event. Patients often report getting sick, sometimes from something as common as infectious mononucleosis (Epstein-Barr virus), and never fully recover. The new research suggests that these infections throw a wrench in the immune system’s ability to quiet itself after the acute infection, to return to a homeostatic balance; the immune response becomes like a car stuck in high gear. “It appears that ME/CFS patients are flush with cytokines until around the three-year mark, at which point the immune system shows evidence of exhaustion and cytokine levels drop,” says Dr. Hornig. “Early diagnosis may provide unique opportunities for treatment that likely differ from those that would be appropriate in later phases of the illness.”

The investigators went to great lengths to carefully screen participants to make sure they had the disease. The researchers also recruited greater numbers of patients whose diagnosis was of relatively recent onset. Patients’ stress levels were standardized; before each blood draw, patients were asked to complete standardized paperwork, in part to engender fatigue. The scientists also controlled for factors known to affect the immune system, including the time of day, season and geographic location where the samples were taken, as well as age, sex and ethnicity/race.

In 2012, W. Ian Lipkin, MD, director of the Center for Infection and Immunity, and colleagues reported the results of a multicenter study that definitively ruled out two viruses thought to be implicated in ME/CFS: XMRV (xenotropic murine leukemia virus [MLV]-related virus) and murine retrovirus-like sequences (designated pMLV: polytropic MLV). In the coming weeks, Drs. Hornig and Lipkin expect to report the results of a second study of cerebrospinal fluid from ME/CFS patients. In separate ongoing studies, they are looking for “molecular footprints” of the specific agents behind the disease—be they viral, bacterial, or fungal—as well as the longitudinal look at how plasma cytokine patterns change within ME/CFS patients and controls across a one-year period, as noted above.

“This study delivers what has eluded us for so long: unequivocal evidence of immunological dysfunction in ME/CFS and diagnostic biomarkers for disease,” says senior author W. Ian Lipkin, MD, also the John Snow Professor of Epidemiology at Columbia’s Mailman School. “The question we are trying to address in a parallel microbiome project is what triggers this dysfunction.”

Co-authors include Andrew F. Schultz, Xiaoyu Che, and Meredith L. Eddy at the Center for Infection and Immunity; Jose G. Montoya at Stanford University; Anthony L. Komaroff at Harvard Medical School; Nancy G. Klimas at Nova Southeastern University; Susan Levine at Levine Clinic; Donna Felsenstein at Massachusetts General Hospital; Lucinda Bateman at Fatigue Consultation Clinic; and Daniel L. Peterson and Gunnar Gottschalk at Sierra Internal Medicine. The authors report no competing interests.

Support for the study was provided by the Chronic Fatigue Initiative of the Hutchins Family Foundation and the National Institutes of Health (AI057158; Northeast Biodefense Center-Lipkin).

About Columbia University’s Mailman School of Public Health

Founded in 1922, Columbia University’s Mailman School of Public Health pursues an agenda of research, education, and service to address the critical and complex public health issues affecting New Yorkers, the nation and the world. The Mailman School is the third largest recipient of NIH grants among schools of public health. Its over 450 multi-disciplinary faculty members work in more than 100 countries around the world, addressing such issues as preventing infectious and chronic diseases, environmental health, maternal and child health, health policy, climate change & health, and public health preparedness. It is a leader in public health education with over 1,300 graduate students from more than 40 nations pursuing a variety of master’s and doctoral degree programs. For more information, please visit www.mailman.columbia.edu.

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Media contact: Tim Paul, Columbia University’s Mailman School of Public Health, 212-305-2676 or tp2111@columbia.edu.

Do Gut Bacteria Rule Our Minds? Cravings, Weight Gain, and Bugs in ME/CFS

Feed me, Seymour. Feed me!

Every once in a while, I come across an article that inspires an "Aha!" moment. The article below is one of them.

Researchers from UC San Francisco have discovered that not only do those trillions of bacteria that live in our guts influence our mood, they can choose what we eat.

Food cravings, especially for sugar, are common in ME/CFS. Formerly, this was chalked up to an overgrowth of Candida, a yeast that thrives on sugar. Dr. Carol Jessop found that after putting her CFS patients on anti-yeast medication, as well as an anti-Candida diet, they made considerable improvement. John Rutter, a well-known composer and ME patient, reported that an anti-Candida regimen was the turning point in his illness.

But, what if the picture is more complicated? What if gut bacteria also play a role in the symptomology of ME/CFS?

Nearly 20 years ago, Lauren Gellman (co-author of Chronic Fatigue Syndrome: A Treatment Guide), and I conducted a survey. Among the questions we asked ME/CFS patients was whether they had recently been treated for infections. Every single one of the respondents answered that they had taken long-term antibiotics prior to contracting ME/CFS.

Antibiotics have saved millions of lives, but, as Oakland, CA gastroentrologist and fecal transplant proponent Dr. Neil Stollman points out, "antibiotics are a scourge." By altering the microbiome with antibiotics, the body's immune system is compromised. And with the proliferation of unhealthy bacteria in our guts, we are prone to inflammation, which can lead to autoimmune disease and colitis. We are also prone to an overgrowth of bacteria in the small intestines known as SIBO, or small intestine bacterial overgrowth. 

Dr. Cheney has proposed that the majority of patients with ME/CFS suffer from SIBO. The symptoms of SIBO include every GI symptom you can think of -  including IBS - as well as exhaustion, insomnia, night sweats, brain fog, muscle weakness, flu-like symptoms, muscle aches, and a horrible night-time malaise. Among gastroenterologists, the cause of SIBO is recognized as antibiotics, which, like the hair of the dog that bit you, are also used to treat SIBO (Xifaxan is preferred).

The test for SIBO is the lactulose breath test. After refraining from eating sugar and milk products, both of which feed the overgrowth, a small amount of lactulose (a synthetic sugar which acts as a mild laxative) is administered. The gases that are produced - methane and hydrogen - are then measured. In simple terms, the more gas produced, the more severe the infection. (You can order this test without a prescription, and administer it yourself.)

So, the question is, what do you crave? Do you crave ice cream, sweets? And, is it you craving those foods, or is it the overgrowth in your small intestine? Nearly all physicians who treat ME/CFS recommend the elimination of sweets. Perhaps the bugs in your gut provide an explanation for why sweets make patients feel worse - and why we crave them.

Even if the elimination of sweets and milk products from your diet doesn't cure you of ME/CFS, there are definitely a few trillion good reasons to refrain from eating them.

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Do gut bacteria rule our minds? In an ecosystem within us, microbes evolved to sway food choices

By Jeffrey Norris 

Press Release: UCSF, August 15, 2014. It sounds like science fiction, but it seems that bacteria within us -- which outnumber our own cells about 100-fold -- may very well be affecting both our cravings and moods to get us to eat what they want, and often are driving us toward obesity.

In an article published this week in the journal BioEssays, researchers from UC San Francisco, Arizona State University and University of New Mexico concluded from a review of the recent scientific literature that microbes influence human eating behavior and dietary choices to favor consumption of the particular nutrients they grow best on, rather than simply passively living off whatever nutrients we choose to send their way.

Bacterial species vary in the nutrients they need. Some prefer fat, and others sugar, for instance. But they not only vie with each other for food and to retain a niche within their ecosystem -- our digestive tracts -- they also often have different aims than we do when it comes to our own actions, according to senior author Athena Aktipis, PhD, co-founder of the Center for Evolution and Cancer with the Helen Diller Family Comprehensive Cancer Center at UCSF.

While it is unclear exactly how this occurs, the authors believe this diverse community of microbes, collectively known as the gut microbiome, may influence our decisions by releasing signaling molecules into our gut. Because the gut is linked to the immune system, the endocrine system and the nervous system, those signals could influence our physiologic and behavioral responses.

"Bacteria within the gut are manipulative," said Carlo Maley, PhD, director of the UCSF Center for Evolution and Cancer and corresponding author on the paper." "There is a diversity of interests represented in the microbiome, some aligned with our own dietary goals, and others not."

Fortunately, it's a two-way street. We can influence the compatibility of these microscopic, single-celled houseguests by deliberating altering what we ingest, Maley said, with measurable changes in the microbiome within 24 hours of diet change.

"Our diets have a huge impact on microbial populations in the gut," Maley said. "It's a whole ecosystem, and it's evolving on the time scale of minutes."

There are even specialized bacteria that digest seaweed, found in humans in Japan, where seaweed is popular in the diet.

Research suggests that gut bacteria may be affecting our eating decisions in part by acting through the vagus nerve, which connects 100 million nerve cells from the digestive tract to the base of the brain.

"Microbes have the capacity to manipulate behavior and mood through altering the neural signals in the vagus nerve, changing taste receptors, producing toxins to make us feel bad, and releasing chemical rewards to make us feel good," said Aktipis, who is currently in the Arizona State University Department of Psychology.

In mice, certain strains of bacteria increase anxious behavior. In humans, one clinical trial found that drinking a probiotic containing Lactobacillus casei improved mood in those who were feeling the lowest.

Maley, Aktipis and first author Joe Alcock, MD, from the Department of Emergency Medicine at the University of New Mexico, proposed further research to test the sway microbes hold over us. For example, would transplantation into the gut of the bacteria requiring a nutrient from seaweed lead the human host to eat more seaweed?

The speed with which the microbiome can change may be encouraging to those who seek to improve health by altering microbial populations. This may be accomplished through food and supplement choices, by ingesting specific bacterial species in the form of probiotics, or by killing targeted species with antibiotics. Optimizing the balance of power among bacterial species in our gut might allow us to lead less obese and healthier lives, according to the authors.

"Because microbiota are easily manipulatable by prebiotics, probiotics, antibiotics, fecal transplants, and dietary changes, altering our microbiota offers a tractable approach to otherwise intractable problems of obesity and unhealthy eating," the authors wrote.

The authors met and first discussed the ideas in the BioEssays paper at a summer school conference on evolutionary medicine two years ago. Aktipis, who is an evolutionary biologist and a psychologist, was drawn to the opportunity to investigate the complex interaction of the different fitness interests of microbes and their hosts and how those play out in our daily lives. Maley, a computer scientist and evolutionary biologist, had established a career studying how tumor cells arise from normal cells and evolve over time through natural selection within the body as cancer progresses.

In fact, the evolution of tumors and of bacterial communities are linked, points out Aktipis, who said some of the bacteria that normally live within us cause stomach cancer and perhaps other cancers.

"Targeting the microbiome could open up possibilities for preventing a variety of disease from obesity and diabetes to cancers of the gastro-intestinal tract. We are only beginning to scratch the surface of the importance of the microbiome for human health," she said.

The co-authors' BioEssays study was funded by the National Institutes of Health, the American Cancer Society, the Bonnie D. Addario Lung Cancer Foundation and the Institute for Advanced Study, in Berlin.

Journal Reference: Joe Alcock, Carlo C. Maley, C. Athena Aktipis. Is eating behavior manipulated by the gastrointestinalmicrobiota? Evolutionary pressures and potential mechanisms. BioEssays, 2014; DOI: 10.1002/bies.201400071

Kindling, Chemical Sensitivities, and ME/CFS

Dr. Jay Streastrunk (now deceased) was a pediatric and adolescent psychiatrist who had a clinical practice in Texas and California. He was known for his explanation of the primary mechanism of multiple chemical sensitivities - "kindling" - and for his willingness to treat patients with an illness that most doctors still don't believe is "real."

Kindling is a neurological mechanism through which repeated exposures to a stimulus can sensitize an individual so that even a small stimulus produces a reaction. In neurological circles, kindling has been linked to seizures. Among allergists, kindling is known as "sensitization." It accounts for why even a hint of peanut can cause anaphylactic shock in an allergic individual. Kindling also is involved in FM and other pain syndromes.

In 2009, Jason et al. proposed that kindling was part of the etiology of ME/CFS. In a paper titled, "Kindling and Oxidative Stress as Contributors to Myalgic Encephalomyelitis/Chronic Fatigue Syndrome", the authors state:

"Viral exposure early in life could trigger an immunologic cascade with significant effects on kindling. The release of TNF-alpha and other mediators could contribute to immunologic sensitization through inflammation and corticosteroid mediation. This then might leave an individual primed to respond in an adverse fashion to a future stressor event through amygdala and hippocampal kindling. The response to a stressor event then might reintroduce an inflammatory response that could contribute to the development of lesions and symptomatology. This could help explain why viral exposure does not necessarily trigger immediate symptomatology."

This model is in keeping with the theory of occult infection - an infection which remains latent, or asymptomatic, until a second stressor is introduced. However, Jason et al. took the model one step further by proposing that the repetition of the exposure over time leads not only to an increasingly sensitive nervous system (which is why relapses often manifest differently from the initial illness), but to a prolonged inflammatory cycle.

Below is Dr. Seastrunk's excellent explanation of kindling. The treatment he recommended for kindling was Neurontin (gabapentin), a neuro-inhibitory drug also favored by Dr. Jay Goldstein. Some ME/CFS patients have reported benefits from gabapentin, however, as with all treatments, responses to gabapentin are mixed.

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KINDLING , FOCAL BRAIN INJURY AND CHEMICAL and ELECTRICAL SENSITIVITY in the production of "Environmental Disease"

by Jay Seastrunk

Kindling

In the 1960's while doing research at Tulane Medical School, I became interested in the correlation between the electrical manifestation of brain activity and behavior. I was fortunate enough to be able to participate in deep electrode long term implant studies in non-psychotic and psychotic individuals. This experience strongly imprinted in me the connection between brain activity and behavior. In reviewing the literature for Dr. R. G. Heath, my department chairman, I came across the "mirror focus" literature.

In 1949, Pope et.al., described the "mirror focus" phenomenon, while working with Penfield on man and monkeys. In "mirror focus" development, an epileptic focus (a mirror focus) is found to develop in the hemisphere opposite to an original epileptic focus, even though there has never been an injury in that hemisphere. This developed focus takes ten to fifteen years to emerge in humans. In 1969, Goddard and two other researchers in the field of epilepsy published an article entitled, "A Permanent Change in Brain Function Resulting from Daily Electrical Stimulation". They were curious as to why an incubation period often elapsed between a traumatic brain injury, and the occurrence of a first seizure, months to years after the injury.

What they discovered was that repeated applications of either chemical or electrical irritants to the brains of animals eventually produce intense seizure discharges, even if each one of the irritating stimulation themselves is incapable of producing a seizure. They discovered that a stimulus to the brain, that ordinarily would produce no change in either the animal's behavior or in the electrical activity of its brain, did produce significant changes in both behavior and electrical activity, if it were repeated and repeated. They called the repeated stimulus "a chronic irritant", and the resulting effect "kindling." In Vietnam veterans, psychosis took fifteen years to emerge following brain injury illustrating that the limbic and/or more subtle behavioral manifestations of brain injury take a long time to emerge perhaps related to the "kindling" phenomena.

In 1992, Bell and her co-workers applied this reasoning to chemical sensitivity. They pointed out that the olfactory system of animals and humans permits access (via the nose) of environmental chemicals directly into the brain. These molecules pass into the entry point of the smell system, called the olfactory bulb. Numerous projections from this part of the brain are present in the upper regions of the nose and permit aromas, perfumes, aromatic hydrocarbons, and solvents to pass into the brain. Even more remarkable than the fact that these molecules pass directly into the brain, is the fact that they can progress neuron by neuron to the furthest reaches of the emotional portion of the brain, called the limbic system.

The limbic system, located primarily in the temporal lobe, serves not only as the location of our emotions, but even more interestingly, it is the location where we organize our information into understandable categories. This is because in animals, smeil has great significance. An odor can mean the difference between food or poison, and friend or foe, so it is reasonable that odors and their significance would be closely linked in the animal brain.

The limbic system, located partially in the temporal lobe, serves, not only as the location of our emotional system, but even more interestingly, as an information organizer, where we process information into understandable perceptions, wheather they are olfactory, visual, tactile, or auditory. Memory with its emotional conections is stored here However, it is tuned into many more inputs than just a single sensory perception. In fact, it seems to be tuned into all possible inputs, whether sensory, imaginative, verbal, or motor. This is why odors, movements, sights, sounds, ideas, or a combination of these can rapidly trigger memories, emotions, and behaviors.

When the limbic temporal lobe is injured, the individual cannot always recall memories at will, even though the memory is still in the brain. Individuals affected with chemical injuries frequently report that they are having memory problems, yet are surprised when psychological tests show no memory damage. This is because the system where the memories are stored, which is analogous to the bookshelves in a library is intact; it is the memory organization and retrieval system or the card catalogue of the library that has been injured.

How does the kindling and the mirror focus phenomenon fit into this? Researchers into epilepsy have long known that the olfactory and limbic systems are particularly susceptible to kindling. In fact, two limbic structures, the amygdala and the hippocampus are frequently used in animals to study epilepsy, because of the ease with which they can be kindled.

This means that individuals whose brains have been injured can be kindled by either repeated low level stimulation of a chemical or electrical irritant, or by a single peak exposure. Thus, an individual will continue to experience more and more effects from exposures too weak to affect a previously unaffected person and possibly become more and more sensitive to weaker and weaker exposures.

Time-Dependent Sensitization

A second mechanism, called time-dependent sensitization, is almost identical to kindling. According to Bell et al. (1992), time-dependent sensitization is very similar to kindling in that an external substance, e.g. a chemical, that has no effect at first on an animal's brain will later produce a major reaction. This sounds almost like kindling, except for a few minor differences. By definition, kindling eventually leads to seizures, whereas time-dependent sensitization does not necessarily lead to seizures. Instead, it can lead to changes in the animal's behavior, its sensations, cognitions, autonomic nervous system responses, vestibuiar (balance) responses, motion responses, and/or or in hs immune or hormonal function.

Another difference is that time-dependent sensitization can occur after a single intense exposure, rather than a few small, repeated ones. After the passage of time, and without further exposure, a new exposure will suddenly produce the altered experience and/or behavior, or alter the immune function.

Finally, time-dependent sensitization shows cross-sensitization, which means that after a given individual is sensitized, other substances, different from the one causing the initial exposure, will now produce the altered experience, and/or behavior or function in a stereotyped way for each individual.

Kindling and time-dependent sensitization answer one of the most mysterious aspects of chemical and electrical sensitivity i.e. who gets affected and why? Another phenomenon, known as cacosmia, must be introduced to understand this

RISK FACTORS FOR CHEMICAL NEUROTOXICITY

On November 13, 1993, over 400 affected workers, health care professionals, and interested labor and management representatives listened to Dr. Bell present her latest findings to a conference hosted by the Washington Toxics Coalition in Seattle, WA. What she and her co-workers suggested is that there is an identifiable group of people more at risk for the development of chemical brain injury than other more resistant individuals.

To be able to identify these individuals, it is first necessary to understand a new term. The new term is cacosmia (ca-COS'-mi-a), which means "an altered sense of smell, accompanied by a tendency to feel ill i.e. nausea, headache, and dizziness from the odor of chemicals at low levels (that have no effect on normals." In other words, cacosmic individuals are the ones who first notice and are affected by the chemical odors in an environment. Six per cent of college students report cacosmia when asked if they develop illness when exposed to pesticides, car exhaust, paint, perfumes, or new carpet. Among the individuals that were studied, women represented 79% of those identified as the most cacosmic.

Among both women and men who were identified as strongly cacosmic, there was a much higher incidence of reported food allergies, self-reported memory loss, and somatic symptoms in general, when compared with noncacosmic subjects.

For electromagnetically sensitive patients, a similar recruitment, sometimes by subliminal visual, or auditory inputs, or by electromagnetic waves themselves, activate a kindled brain focus, causing it to fire, producing the characteristic, stereotyped, repetitive symptoms of that individual's "reaction".

A second risk factor appears to be stress. Ester Stemberg described how the central nervous system affects the immune system through endocrine, paracrine, and neuronal mechanisms. Bell, also, points out that one of the stress hormones in the brain, CRH, cannot only itself produce kindling, but when present in above normal amounts, makes it more likely that other external stimuli will induce kindling. Stress and sleep deprivation have long been known to increase epileptic seizures.

I feel that a third necessary factor is focal brain injury related to trauma, infection, or toxic insult. The location of this injury determines the scope of the repetitive, stereotyped symptoms, which becomes the "reaction" kindled by the external stimulus whether chemical, electrical, and/or stress and sleep deprived related.

Conclusions

1 It appears that perhaps some of the mystery of chemical sensitivity syndrome is beginning to disappear. Repeated small exposures to inhaled toxins, chemical or visual kindling, auditory, and/or electrical stimulation, or single overwhelming exposures, acting on focal injuries can bring about sensitization of the brain's limbic system injury.

2. Because the brain's limbic system modulates emotions and memory organization systems, emotional and memory symptoms will be common features of the disease. This area of the brain also controls balance, gastrointestinal motility, the autonomic nervous system, and auditory and visual integration of stimuli as well as memory

3. Repeated exposures after the kindling or sensitization of the focus has occurred will produce effects out of proportion to the intensity of the exposure.

4 Cacosmic people seem more at risk than non-cacsomic people; but this has not yet been proved by a prospective study.

5. Stress may play some role in who becomes affected, but how big a role is still uncertain. Stress definitely increases the occurrence of "reactions", as does sleep deprivation due to its effect on focal brain irritability.

6. Because a fundamental brain mechanism is involved in the production of chemical sensitivity, continued exposure of individuals without protection or treatment is sure to increase the number of affected individuals and the severity of the symptoms in any particular individual.

TREATMENT

To be effective, treatment must interrupt these processes. Certainly avoidance of the stimuli can stop the setting off of the focal firing either directly or by stopping the kindling. Medications that stabilize the irritated cell decreasing its sensitivity to the kindling stimulus would be helpful. In this approach the amino acid anticonvulsant gabapentin has been very promising in our experience. Decreasing stress and improving sleep will also be beneficial. Removing any toxin that is still present in the brain should also decrease cell irritability. Desensitizations of all types, allergic, and behavioral, seem to provide benefit.

References

Bell, I., Miller, C., & Schwartz, G. An olfactory-limbic model of multiple chemical sensitivity syndrome, possible relationships to kindling and affective spectrum disorders. Biol. Psychiatry. 1992, 32: 218-242.

Bell L Schwartz C, Peterson A, et al. Possible time dependent sensitization to Xenobiotics: Self-reported illness from chemical odors, foods, and opiate drugs in an older population. Archives of Environmental Health. 1993, 48:315-327, 60p cit #4 p. 316.

Goddard G., Mclntyre D, Leech C. A permanent change in brain function resulting from daily electrical stimulation Exp Neurology 1969,25:295-330

Heath R Correlation of brain function with emotional behavior. Biol Pychiatry. 1976:11 463-480

McNamara J, Bonhaus D, Shin C, et al. The kindling model of epilepsy: a critical review CR Clin Neurobiol 1985;l:341-391

Monroe R. Limbic Ictus and Atypical Psychoses. Jwr of Nervous and Mental Disease 1982;170 #12:711-716.

Morrell F. Experimental epilepsy in animals. Arch Neural 1959,1:141-147. Morrell F Secondary epileptic lesions Epilepsia 1960,1538-560.

Pope A. Morris AA, Jasper H. et al. Histochemical and action potential studies on epileptogenic areas of cerebral cortex in man and the monkey. Res Publ Assoc Res Nerv Mem Dis 1946:26:218-233.

Schwartzkroin, P. A. Epilepsy: Models. Mechanisms, and Concepts Cambridge University Press 1993,27-47;40p Cit #2 pg.221.

Stemberg EM The role of the hypothalamic-pituitary-adrenal axis in susceptibility to autoimmune/inflammatory disease Immunomethods Aug. 1994 5(1): 73-8

Sutula T Experimental models of temporal lobe epilepsy, new insights from the study of kindling and synaptic reorganization Epilepsia 1990;31 (suppl. 3): S45-S5Q.

USF- led study suggests some chronic fatigue syndrome patients may benefit from anti-herpesvirus drug treatment

Press Release: Morsani College of Medicine, July 25, 2013

Tampa, FL (July 25, 2013) – Many experts believe that chronic fatigue syndrome (CFS) has several root causes including some viruses.

Now, lead scientists Shara Pantry, Maria Medveczky and Peter Medveczky of the University of South Florida’s Morsani College of Medicine, along with the help of several collaborating scientists and clinicians, have published an article  in the Journal of Medical Virology suggesting that a common virus, Human Herpesvirus 6 (HHV-6), is the possible cause of some CFS cases.

Over 95 percent of the population is infected with HHV-6 by age 3, but in those with normal immune systems the virus remains inactive. HHV-6 causes fever and rash (or roseola) in infants during early childhood, and is spread by saliva. In immunocompromised patients, it can reactivate to cause neurological dysfunction, encephalitis, pneumonia and organ failure.

“The good news reported in our study is that antiviral drugs improve the severe neurological symptoms, including chronic pain and long-term fatigue, suffered by a certain group of patients with CFS,” said Medveczky, who is a professor of molecular medicine at USF Health and the study’s principal investigator. “An estimated 15,000 to 20,000 patients with this CFS-like disease in the United States alone may ultimately benefit from the application of this research including antiviral drug therapy.”

The link between HHV-6 infection and CFS is quite complex. After the first encounter, or “primary infection,” all nine known human herpesviruses become silent, or “latent,” but may reactivate and cause diseases upon immunosuppression or during aging. A previous study from the Medveczky laboratory showed that HHV-6 is unique among human herpesviruses; during latency, its DNA integrates into the structures at the end of chromosomes known as telomeres.

Furthermore, this integrated HHV-6 genome can be inherited from parent to child, a condition commonly referred to as “chromosomally integrated HHV-6,” or CIHHV-6. By contrast, the “latent” genome of all other human herpesviruses converts to a circular form in the nucleus of the cell, not integrated into the chromosomes, and not inheritable by future generations.

Most studies suggest that around 0.8 percent of the U.S. and U.K. population is CIHHV6 positive, thus carrying a copy of HHV-6 in each cell. While most CIHHV-6 individuals appear healthy, they may be less able to defend themselves against other strains of HHV-6 that they might encounter. Medveczky reports that some of these individuals suffer from a CFS-like illness. In a cohort of CFS patients with serious neurological symptoms, the researchers found that the prevalence of CIHHV-6 was over 2 percent, or more than twice the level found in the general public. In light of this finding, the authors of the study suggest naming this sub-category of CFS “Inherited Human Herpesvirus 6 Syndrome,” or IHS.

Medveczky’s team discovered that untreated CIHHV-6 patients with CFS showed signs that the HHV-6 virus was actively replicating: determined by the presence of HHV-6 messenger RNA (mRNA), a substance produced only when the virus is active. The team followed these patients during treatment, and discovered that the HHV-6 mRNA disappeared by the sixth week of antiviral therapy with valganciclovir, a drug used to treat closely related cytomegalovirus (HHV-5).  Of note, the group also found that short-term treatment regimens, even up to three weeks, had little or no impact on the HHV-6 mRNA level.

The investigators assumed that the integrated virus had become reactivated in these patients; however, to their surprise, they found that these IHS patients were infected by a second unrelated strain of HHV-6.

The USF-led study was supported by the HHV-6 Foundation and the National Institutes of Health.

Further studies are needed to confirm that immune dysregulation, along with subsequent chronic persistence of the HHV-6 virus, is the root cause of the IHS patients’ clinical symptoms, the researchers report.

Article citation: “Persistent human herpesvirus-6 infection in patients with an inherited form of the virus." Shara N. Pantry, Maria M. Medveczky, Jesse H. Arbuckle,  Janos Luka,Jose G. Montoya, Jianhong Hu, Rolf Renne, Daniel Peterson, Joshua C. Pritchett, Dharam V. Ablashi, andPeter G. Medveczky; Journal of Medical Virology; published online July 25, 2013; DOI: 10.1002/jmv.23685