Researchers are making headway toward finding evidence of chronic fatigue syndrome and how it may change the brain.
Ronald W. Davis, a Stanford University genetics researcher who was instrumental in the Human Genome Project, is heading up a new research center at Stanford University, which is rapidly becoming a nexus for chronic fatigue research.
Davis — whose son, Whitney Dafoe, has severe chronic fatigue syndrome — believes the answers lie in finding molecular biomarkers, which are characteristics or substances that indicate the person has a particular biological condition or disease. A specific marker might lead to a blood test that can definitively diagnose and potentially treat chronic fatigue, Davis said. So far, chronic fatigue has not shown its face through conventional blood markers that indicate inflammation in the body or that show the presence of a specific infection.
Davis and his team plan to use technologies developed for the Human Genome Project to sequence the entire genome of chronic fatigue patients, including 1,600 mitochondrial genes, more than 20,000 other genes and control regions that regulate genes. They hope to identify proteins that are found in immune cells, blood and spinal fluid; search for infectious agents in blood, bone marrow, spinal fluid and saliva and changes to gastrointestinal tract flora; and find evidence of autoimmune responses. The research could reveal DNA sequences that are altered in chronic fatigue patients.
The detailed approach is more comprehensive than that of other research, which has only looked at a fraction of the genes, according to the center’s website.
The center’s research will also focus on a large number of the most severely ill patients, who often have disruptions to multiple body systems where a pathogen or genetic alteration may be lurking, Davis said. The research will look at patients who have responded positively to drug treatments and those who have failed to respond, he said.
Researchers have known for many years that the onset of chronic fatigue is often preceded by a viral or infection-like illness, according to the Stanford University School of Medicine’s Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Initiative, another university research arm.
The disease may have multiple causes. Two main theories are that the disease is caused by a pathogen or by an immune-system reaction to a pathogen, according to a Stanford research team led by Dr. Jose G. Montoya, professor of medicine in the Division of Infectious Diseases. Montoya has studied chronic fatigue patients for seven years through the ME/CFS Initiative.
Focusing on organs and body systems most likely to be involved in the disease, Montoya and his team work with researchers and physicians in departments such as immunology, brain research, cardiology, genetics and pathogen discovery to pursue clues, he said.
In one study, Montoya and lead researcher Mady Hornig of Columbia University looked at 298 chronic fatigue patients and 348 people without the disease, and what they found was surprising: inflammation
Patients in the early stages of chronic fatigue had elevated levels of certain cytokines — chemical messengers that regulate inflammation. The most prevalent cytokine was interferon gamma, which has been associated with fatigue from viral infections, including mononucleosis.
Patients who had the disease for three years or less had the elevated immune molecules, but persons with the disease for more than three years showed low levels of the cytokines, which could be evidence that the immune system is exhausted, according to the research.
Finding the cytokines provided proof that chronic fatigue is biological and not merely psychological, and it offers hope that early treatment might affect the outcome of the disease.
In a separate study, Montoya and Michael Zeineh, Stanford associate professor of radiology, found significant differences between the brains of chronic fatigue patients and persons without the disease. Brain-imaging studies showed that overall “white matter” — long nerves that carry signals to the “gray matter” parts of the brain, which process information — were abnormal. Chronic fatigue syndrome appeared to involve chronic inflammation, according to their research.
The abnormality was located in the right hemisphere of the brain, which connects to the frontal and temporal lobes. The amount of abnormality also correlated to the severity of the patient’s condition, they said.
The gray matter in those areas of the brain was also thickened, according to their Oct. 29, 2014, study, which was published in the journal Radiology.
But Montoya said they do not know if the left side of the brain is also inflamed, and the right-side aberrations are thickened because of a compensatory reaction, he said.
There are also two schools of thought regarding whether chronic fatigue is caused by a single disease that causes multiple symptoms or if there are subsets of patients afflicted by are variety of agents, he said.
“With AIDS, there are different manifestations of the disease, but they are all caused by a single virus,” he said by way of example.
Several infectious diseases have been associated with the onset of chronic fatigue in some patients, including Epstein-Barr virus (glandular fever), which is associated with mononucleosis, Coxiella burnett (Q fever), enteroviruses (which affect the gastrointestinal tract) and Herpesvirus 6. Montoya said he has had several patients whose chronic fatigue started with the H1N1 influenza.
“There’s no question that different agents have been found,” he said.
Montoya and Dr. Andreas Kogelnik of the Open Medicine Institute in Mountain View have also looked at the use of anti-viral medications in some chronic fatigue patients. Their 2012 study of 61 patients given the anti-viral drug valganciclovir found that 52 percent experienced at least a 30 percent improvement in physical or cognitive functioning. Among these, 59 percent had physical improvements and 81 percent improved cognitively.
Their 2013 double-blind study with valganciclovir against a placebo involved 30 chronic fatigue patients who had elevated antibodies against human herpesvirus 6 and Epstein-Barr, found that patients who received the drug had a greater improvement in mental fatigue, fatigue severity and cognitive function within the first three months. The benefits continued for the remaining nine months. The patients’ white blood cells and other immune-system responses also improved, according to the study, which was published in the Journal of Medical Virology.
Davis is working with numerous collaborators across many fields, hoping the collaborative effort will attract the best minds in their fields.
“This is probably one of the last major diseases we know nothing about. This is your last chance to be a pioneer,” he said.
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Having suffered with ME for over 10 years, the first thing i noticed was brain fog & my ability to problem solve was impaired. Apart from the constant pain i was in i was pushing harder each day to overcome my difficulties for the last two years until o could no longer carry on with my business of which i was paid extremely well…! To think i would rather sit on my back side & claim i needed support which wasn’t on hand & to see my saving dwindling away whilst no medical professional could give me a definitive answer for the exhaustion & pain i was in was devastating. I became bad bound for 8 months, unable to read or write through cognition short term memory failure. Over time i read single words as a child learning to read but things started to sink into my brain & i soon believed something had changed my bodies DNA within my brain, which i still believe. At times i liken it to altimeters or Dementia with flu & muscle with tendon ligament damage. Each year my abilities i feel are improving, but my ability to pace myself has not so within 2 hours of activity i am fatigued. At risk of losing my sanity, my home & having lost my old life, thought of suicide cross my mind but i am ever hopeful of society developing a better understanding of how debilitating this condition is & possibly recovering a cure.
I live in the UK, having read my above comment with embarrassment i thought i should make a better effort to explain myself more clearly. This is because of the effect of brain fog…!
Having suffered with ME for over 10 years, the first thing i noticed was brain fog & my ability to problem solve was impaired. Apart from the constant pain i was in, i was pushing harder each day to overcome my difficulties for the last two active years until i could no longer carry on with my business, of which i was paid extremely well…! To think i would rather sit on my back side & claim i needed support! which wasn’t on hand & to see my savings dwindling away whilst no medical professional could give me a definitive answer for the exhaustion & pain i was in, was devastating. I became bed bound for 8 months, i found i was unable to read or write through cognition short term memory failure. Over time i read single words, as a child would when learning to read, slowly things started to sink into my brain & i soon believed something had changed my bodies DNA within my brain, which i still believe. At times i liken it to altimeters or Dementia with flu & muscle with tendon ligament damage. Each year my abilities i feel are improving, but my ability to pace myself has not, so within 2 hours of activity i am fatigued. With the thought of being at risk of losing my sanity, my home & having lost my old full active life, i have had thoughts of suicide crossing my mind, but i am ever hopeful of society developing a better understanding of how debilitating this condition is, & possibly recovering when a cure is found.
Weekly, can you please combine these comments with the main thread? Don’t know why this separate thread was started.
Dear Ms. Dremann,
This is a very good article. Thank you! But, two things were like nails on the chalkboard to me:
(1) this disease is called “Myalgic Encephalomyelitis” and “Chronic Fatigue *Syndrome*”, but NOT “chronic fatigue.” “Chronic fatigue” is just a symptom of many diseases and non-disease states. Using this term has caused an incredible amount of confusion over the years. Let’s end the confusion. Thank you.
(2) it was not “surprising” that Montoya found inflammation in brains of people with ME. This has been found since the 1980s, to my knowledge, in every study which looked for it.
Do you mind correcting this article? Thank you so much for your consideration.
Justin Reilly, JD
As a veteran journalist myself I would like to congratulate Ms. Dremann on wrapping up this subject matter in concise form but with great understanding. Were all journalists equally conscientious we might well be closer to a cure.
I do, however, echo Justin Reilly’s objection to calling the disease “chronic fatigue.” As he notes, this compound noun is a symptom of many, many chronic illnesses — cancer, multiple sclerosis, Sjögren’s syndrome, lupus, rheumatoid arthritis and more, and therefore not suitable as a name for any one.
A bit of history may be helpful here. Going back into the past century, this disease had been known as everything from “Iceland Disease” — after an outbreak there — to “Benign Poliomyelitis” (for its lack of immediate fatalities.)
A descriptive official name, “Myalgic Encephalomyelitis,” (M.E.) originated in a 1955 editorial in the prestigious British Medical Journal. This appeared following the infamous outbreak of M.E. at London’s Royal Free Hospital, which had struck down staff en masse.
The World Health Organization (WHO) made the name official internationally in 1968, and WHO staff assigned it the code 93.3. This put it within the category of neurological diseases, as it then was already known to affect spinal cord and brain tissues.
Yet Americans – including, alas, the majority of their doctors — know the disease only by the misleading and dismissive moniker “Chronic Fatigue Syndrome.” This is so because the Centers for Disease Control and Prevention (CDC) had re-christened it so in 1988, and put the full force of its many publications, studies and releases behind embedding it in the national mind.
Why? Surely someone must have noticed that this would appear a crass gesture of “Ugly American” intellectual imperialism, apart from other improprieties.
Propaganda is the answer. Beginning in the winter of 1984-85, when a large outbreak of the disease mysteriously struck Incline Village, Nevada, on the northern shore of Lake Tahoe, scary rumors had flown. Would the new Tahoe disease turn out to be a super-flu, or perhaps mononucleosis on steroids?
This was not good for the economy. The Tahoe area economy, to be specific. Tahoe attracts three million visitors annually, fueling a multi-billion dollar economy based on real estate and tourism. Rumors scare away tourists, second home folk and dollars.
Agencies of the Federal government, namely CDC and National Institutes of Health (NIH), were enlisted to subdue the growing panic. They plunged in. An NIH viral expert, for example, encouraged edits to CDC reporting that would delete mention of seizures among the stricken.
Finally, in 1988, a committee meeting was set to consider the disease and its name. It would include international experts familiar with Myalgic Encephalomyelitis who clearly identified the Tahoe ailment as such. The name “Chronic Fatigue Syndrome” (CFS), employed in some US material since 1986, would be under discussion as a happily anodyne alternative to the grim-sounding Myalgic Encephalomyelitis.
Speaking generally, of course, no corporate chief or government administrator in her or his right mind will leave the outcome of an important meeting to spur-of-the-moment interactions among participants. Nor did this meeting seem to have been left to chance. The name “Chronic Fatigue Syndrome,” suggesting only mild discomfort on the part of its victims — as opposed to the cancers, heart failure and overwhelming disability that constitute the reality — was duly voted in. Three committee members, all with wide experience of ME, felt so strongly their dissent that they resigned on the spot and walked out of the meeting in apparent fury.
Tahoe recovered rapidly. The patients have not.
At present the NIH and CDC often combine names, referring to “ME/CFS” and following pressures and initiatives from outside.
Yet despite apparent peace the NIH most peculiarly has initiated a purge of the name Myalgic Encephalomyelitis. Observer minds boggled when the Institute of Medicine (IOM) committee hired in 2013 by NIH to assess “ME/CFS” announced its conclusions ahead of time in early 2015; they include the proposed new name “Systemic Exertion Intolerance Disorder” (SEID.) There wasn’t really much encephalomyelitis to be found in patients, IOM reasoned, after having excluded Stanford research to make the point stick.
It is beginning to emerge, however, that engineering the new name may have been still another degree less kosher. At the May 29, 2015 London conference of British M.E. charity Invest in M.E., one speaker announced truly gobsmacking news: an IOM insider had informed him that, contrary to Institute procedure, the committee had been ordered to get rid of the name Myalgic Encephalomyelitis. And so the prestigious IOM committee papered over the name studies have shown to make medical professionals and public alike most inclined to take the disease seriously – thereby maximizing help for patients. By logic one must reason that the purpose of SEID was premeditated to discourage help and care for patients.
Hey everyone,
The main page of comments is here:
http://www.paloaltoonline.com/square/2015/07/10/living-on-empty
A troll whose post has since been removed started this separate thread. Please comment to the original thread so everyone gets the benefit of all the comments!
“Examination of Single Nucleotide Polymorphisms (SNPs) in Transient Receptor Potential (TRP) Ion Channels in Chronic Fatigue Syndrome Patients”
This study explains why so many people with Chronic Fatigue Syndrome develop Postural Orthostatic Tachycardia Syndrome (POTS) as well as allergies, pain, gut problems, and chemical sensitivity. The study findings are compatible with all the recent studies that show small but significant changes to the brains of CFS patients.
You can download the paper here.
http://www.la-press.com/examination-of-single-nucleotide-polymorphisms-snps-in-transient-recep-article-a4824
Dr. Paul R. Cheney, who runs the Cheney Clinic in Asheville, NC has been focused on this illness since the first reported outbreaks in Incline Village in the mid 1980’s. He is a leading researcher and clinical physician and has brought many people back from this illness. If you’re extremely ill, you should contact his clinic. He saved my life.
Here in the UK we are using dried chicken bones and white feathers to scare away bad spirits
“… with valganciclovir against a placebo involved 30 chronic fatigue patients who had elevated antibodies …”
This should read: “… with valganciclovir against a placebo involved 30 Chronic Fatigue Syndrome patients who had elevated antibodies ….”
“Chronic Fatigue Syndrome is a diagnosis; “chronic fatigue” is a symptom.
I bet you don’t substitute “thirsty” for “diabetic.”
By shortening the name of this illness and placing it in lower case letters you are leading people to believe that tiredness and CFS are the same thing.
Please correct the article. There’s really no reason to publish good information if you’re going to pair it with careless writing that perpetuates stereotypes.