Discovery could lead to faster diagnosis for some chronic fatigue syndrome cases

For the first time, researchers have landed on a potential diagnostic method to identify at least a subset of patients with chronic fatigue syndrome (CFS), a complex disorder with no known definitive cause or cure.

In a pilot study of six patients, scientists detected specific antibodies linked to latent Epstein-Barr virus reactivation in blood samples from people who had experienced classic CFS symptoms and responded to antiviral treatment. Control blood samples from 20 healthy people showed no such antibodies.

The research team, led by scientists from Ohio State University and Oakland University William Beaumont School of Medicine, acknowledges that the number of patients is small. But the researchers say the study’s power rests in their access to 16 months of blood samples for each patient — a collection allowing for an unprecedented longitudinal look at CFS.

The researchers plan to move forward with development of a clinical laboratory test that can detect these antibodies in blood samples.

The study is published in the Nov. 14 issue of the journal PLOS ONE.

The Epstein-Barr virus is a human herpes virus that causes infectious mononucleosis and several different types of tumors. An estimated 95 percent of Americans have been infected with the virus by adulthood, according to the Centers for Disease Control and Prevention (CDC), but fewer than half have experienced an active illness. Once a person is infected, the virus remains dormant in the body, and can be reactivated without causing symptoms of illness.

In these six patients, the study suggests that a latent Epstein-Barr virus had begun to reactivate, but that the newly awakened virus never reached its full potential to take over its host cells. That partial reactivation advanced enough to generate at least two viral proteins, DNA polymerase and dUTPase, and these patients produced antibodies specifically designed to identify and neutralize those proteins for more than a year.

The scientists theorize that even in the absence of a complete active infection, these viral proteins’ ability to induce inflammatory chemical signals causes enough immune system chaos to lead to CFS. The disorder’s main symptom is profound fatigue for at least six months that does not improve with rest, and is accompanied by problems that can include weakness, muscle pain, impaired memory and depression. Because the illness mimics many other disorders, diagnosis is difficult. An estimated 1 million Americans have CFS, but experts believe only 20 percent are diagnosed.

The study’s senior researchers agree that the work should be repeated in more patients “to confirm that these observations are real,” said virologist Ron Glaser, director of the Institute for Behavioral Medicine Research at Ohio State and a co-author of the study. “But finally, after more than 20 years, this is at least something to go on.”

Glaser’s primary collaborators on this work are Marshall Williams, professor of molecular virology, immunology and medical genetics at Ohio State, and A. Martin Lerner, a professor of internal medicine at Oakland University William Beaumont School of Medicine.

Ohio State and Lerner’s private practice, CFS LLC, have applied for a patent for the diagnostic method.

Glaser and Williams first published a paper in 1988 suggesting that these two viral proteins associated with partially reactivated Epstein-Barr virus could function as biomarkers for certain illnesses, including CFS. Meanwhile, Lerner became severely ill in 1986 and struggled for 10 years with CFS symptoms before treatment with antivirals dramatically improved his health.

Lerner, an infectious diseases specialist, runs his private CFS practice in Michigan, and his long-term tracking of patients’ characteristics and response to treatment made this longitudinal research possible.

The fact that CFS patients experience different symptoms and multiple types of viral and bacterial infections has led researchers to believe CFS potentially has numerous causes. That lack of uniformity also complicates the diagnostic process and development of treatments.

“Part of the problem in trying to identify an agent or biomarkers for chronic fatigue syndrome is the extreme variability among people who say they have CFS. How to sort that out has held the field back a lot of years,” said Glaser, who has studied the Epstein-Barr virus (EBV) for decades.

Lerner had long ago separated 142 of his patients into two groups: those who had tested positive for various antibodies against three types of herpes viruses and responded to months-long treatment with one of two types of antivirals, and a smaller group that had viral infections and a variety of co-infections who showed minimal response to antiviral treatment. As part of this tracking, he collected multiple blood serum samples for more than a year from each patient.

From those patients, he selected blood samples from six for this study. Five had been identified as an Epstein-Barr virus subset, and the sixth had Epstein-Barr virus and a bacterial co-infection. For comparison, researchers collected samples from 20 healthy people matched to the six CFS patients for age and sex.

Lerner, too, had independently hypothesized that CFS patients might be experiencing partial virus reactivation. Patients might test negative for the most active antibodies required to fight a virus, but could still recover from CFS after long-term antiviral treatment. One antiviral he uses is known to inhibit DNA polymerase, which would halt Epstein-Barr virus reactivation in its tracks.

With the CFS patients’ and control blood samples in hand, Williams used a highly sensitive laboratory method to detect whether they contained antibodies to the two target Epstein-Barr viral proteins, DNA polymerase and dUTPase, that are produced early in the process of viral reactivation.

Overall, 78.8 percent of the serum samples from the six CFS patients were positive for antibodies against DNA polymerase and 44.2 percent were positive for antibodies against dUTPase. No antibodies to these two proteins were detected in the 20 control samples.

“Every one of the six had antibodies to DNA polymerase or EBV dUTPase and those antibodies persisted over some 408 days,” Lerner said. “And the antibody levels were extraordinarily high.” High levels of antibodies circulating in the blood suggest long-term immune activation against those proteins.

Williams noted that the levels might be less significant than the antibodies being present in the first place.

“If you look at most healthy individuals, they wouldn’t have any reason to have an antibody against either of these proteins,” he said. “The antibodies alone are a good differentiator.”

This work was partially supported by the National Institutes of Health.

Additional co-authors include Maria Ariza of the Department of Molecular Virology, Immunology and Medical Genetics and Stanley Lemeshow, dean of the College of Public Health, both at Ohio State; Leonard Jason of DePaul University; Safedin Beqaj of Pathology Inc., in Torrance, Calif.; and James Fitzgerald of the University of Michigan School of Medicine.

Journal Reference: A. Martin Lerner, Maria E. Ariza, Marshall Williams, Leonard Jason, Safedin Beqaj, James T. Fitzgerald, Stanley Lemeshow, Ronald Glaser. Antibody to Epstein-Barr Virus Deoxyuridine Triphosphate Nucleotidohydrolase and Deoxyribonucleotide Polymerase in a Chronic Fatigue Syndrome Subset. PLoS ONE, 2012; 7 (11): e47891 DOI: 10.1371/journal.pone.0047891

 

Source: Ohio State University. “Discovery could lead to faster diagnosis for some chronic fatigue syndrome cases.” ScienceDaily. ScienceDaily, 14 November 2012. https://www.sciencedaily.com/releases/2012/11/121114171708.htm

 

Spinal fluid proteins distinguish Lyme disease from chronic fatigue syndrome

Patients who suffer from Neurologic Post Treatment Lyme disease (nPTLS) and those with the chronic fatigue syndrome report similar symptoms. However unique proteins discovered in spinal fluid can distinguish those two groups from one another and also from people in normal health, according to new research conducted by a team led by Steven E. Schutzer, MD, of the University of Medicine and Dentistry of New Jersey — New Jersey Medical School, and Richard D. Smith, Ph.D., of Pacific Northwest National Laboratory.

This finding, published in the journal PLoS ONE, also suggests that both conditions involve the central nervous system and that protein abnormalities in the central nervous system are causes and/or effects of both conditions.

The investigators analyzed spinal fluid from three groups of people. One group consisted of 43 patients who fulfilled the clinical criteria for chronic fatigue syndrome (CFS). The second group consisted of 25 patients who had been diagnosed with, and treated for, Lyme disease but did not completely recover. The third group consisted of 11 healthy control subjects. “Spinal fluid is like a liquid window to the brain,” says Dr. Schutzer. By studying the spinal fluid, the research team hoped to find abnormalities that could be used as markers of each condition and could lead to improvements in diagnosis and treatment.

Taking advantage of previously unavailable methods for detailed analysis of spinal fluid, the investigators analyzed the fluid by means of high powered mass spectrometry and special protein separation techniques. They found that each group had more than 2,500 detectable proteins. The research team discovered that there were 738 proteins that were identified only in CFS but not in either healthy normal controls or patients with nPTLS and 692 proteins found only in the nPTLS patients. Previously there had been no available candidate biomarkers to distinguish between the two syndromes, nor even strong evidence that the central nervous system is involved in those conditions.

This research represents the most comprehensive analysis of the complete CSF proteome (collection of proteins) to date for both Chronic Fatigue Syndrome and Neurologic Post Treatment Lyme disease (nPTLS). Prior to this study, many scientists believed that CFS was an umbrella category that included nPTLS. However these results call those previous suppositions into question.

According to Dr. Schutzer, spinal fluid proteins can likely be used as a marker of disease, and this study provides a starting point for research in that area. “One next step will be to find the best biomarkers that will give conclusive diagnostic results,” he says. “In addition, if a protein pathway is found to influence either disease, scientists could then develop treatments to target that particular pathway.”

“Newer techniques that are being developed by the team will allow researchers to dig even deeper and get more information for these and other neurologic diseases,” says Dr. Smith. “These exciting findings are the tip of our research iceberg”

Journal Reference: Steven E Schutzer, Thomas E Angel, Tao Liu, Athena A Schepmoes, Therese R Clauss, Joshua N Adkins, David G Camp, Bart K Holland, Jonas Bergquist, Patricia K Coyle, Richard D Smith, Brian A Fallon, Benjamin H Natelson. Distinct Cerebrospinal Fluid Proteomes Differentiate Post-Treatment Lyme Disease from Chronic Fatigue Syndrome. PLoS ONE, 23 Feb 2011 DOI: 10.1371/journal.pone.0017287

 

Source: Public Library of Science. “Spinal fluid proteins distinguish Lyme disease from chronic fatigue syndrome.” ScienceDaily. ScienceDaily, 23 February 2011. https://www.sciencedaily.com/releases/2011/02/110223171235.htm

 

Chronic Fatigue Syndrome Linked To Impaired Stress Response

Subtle alterations of a hormonal stress response system called the HPA axis may play a role in chronic fatigue syndrome, according to a study in the November/December issue of Psychosomatic Medicine.

A smoothly functioning hypothalamus-pituitary-adrenal, or HPA, axis helps the body remain stable under physiological and psychological stress through the actions of three hormones. First, the brain portion called the hypothalamus secretes a hormone that stimulates the pituitary gland to secrete a second hormone. This second hormone causes the adrenal glands to create cortisol.

Problems can occur at any point in this process and result in a variety of diseases. A research team led by Jens Gaab, Ph.D., of the Center for Psychobiological and Psychosomatic Research at the University of Trier in Trier, Germany; and the Institute of Psychology at the University of Zürich in Switzerland are proposing that chronic fatigue syndrome may be one of them.

Chronic fatigue syndrome is characterized by debilitating fatigue that can include including muscle aches, low-grade fever and sleep disturbances. Its cause is not understood.

Gaab and colleagues recruited approximately 40 study participants between the ages of 30 and 50. Half of the participants were chronic fatigue sufferers and the other half were healthy volunteers. All participants completed questionnaires measuring fatigue, depression and coping skills.

To examine the HPA axis in action, participants were given blood, cardiovascular and saliva tests before and after taking two stress tests. The first, a psychosocial stress test, involved preparing for a fake job interview and completing an arithmetic problem before an audience while under the impression they were being videotaped. The second test measured physical stress on a stationary bicycle.

Participants were also given a series of insulin injections known as the insulin tolerance test. “The ITT is considered the gold standard for testing the integrity of the entire HPA axis,” Gaab says.

The researchers found significantly lower response levels of one of the HPA hormones, called ACTH, among the chronic fatigue patients compared with the healthy volunteers, during both stress tests as well as the ITT test. In fact, the chronic fatigue patients had significantly lower levels of the hormone before the testing even began.

“These results suggest that on a central level, subtle dysregulations of the HPA axis exist” in chronic fatigue syndrome patients, Gaab says, adding that future studies should include repeated evaluation of the HPA axis over the course of the syndrome.

Gaab and colleagues note that the possible role of cortisol in chronic fatigue syndrome still merits investigation, as low doses of hydrocortisone have shown some positive results in chronic fatigue patients.

Source: Center For The Advancement Of Health. “Chronic Fatigue Syndrome Linked To Impaired Stress Response.” ScienceDaily. ScienceDaily, 27 November 2002. https://www.sciencedaily.com/releases/2002/11/021126202215.htm

Brain abnormalities found in chronic fatigue patients

An imaging study by Stanford University School of Medicine investigators has found distinct differences between the brains of patients with chronic fatigue syndrome and those of healthy people.

The findings could lead to more definitive diagnoses of the syndrome and may also point to an underlying mechanism in the disease process.

It’s not uncommon for CFS patients to face several mischaracterizations of their condition, or even suspicions of hypochondria, before receiving a diagnosis of CFS. The abnormalities identified in the study, to be published Oct. 29 in Radiology, may help to resolve those ambiguities, said lead author Michael Zeineh, MD, PhD, assistant professor of radiology.

“Using a trio of sophisticated imaging methodologies, we found that CFS patients’ brains diverge from those of healthy subjects in at least three distinct ways,” Zeineh said.

CFS affects between 1 million and 4 million individuals in the United States and millions more worldwide. Coming up with a more precise number of cases is tough because it’s difficult to actually diagnose the disease. While all CFS patients share a common symptom — crushing, unremitting fatigue that persists for six months or longer — the additional symptoms can vary from one patient to the next, and they often overlap with those of other conditions.

Scientific Challenge

“CFS is one of the greatest scientific and medical challenges of our time,” said the study’s senior author, Jose Montoya, MD, professor of infectious diseases and geographic medicine. “Its symptoms often include not only overwhelming fatigue but also joint and muscle pain, incapacitating headaches, food intolerance, sore throat, enlargement of the lymph nodes, gastrointestinal problems, abnormal blood-pressure and heart-rate events, and hypersensitivity to light, noise or other sensations.”

The combination of symptoms can devastate a patient’s life for 10, 20 or even 30 years, said Montoya, who has been following 200 CFS patients for several years in an effort to identify the syndrome’s underlying mechanisms. He hopes to accelerate the development of more-effective treatments than now exist. (A new Stanford Medicine magazine story describes the study in more detail.)

“In addition to potentially providing the CFS-specific diagnostic biomarker we’ve been desperately seeking for decades, these findings hold the promise of identifying the area or areas of the brain where the disease has hijacked the central nervous system,” Montoya said.

“If you don’t understand the disease, you’re throwing darts blindfolded,” said Zeineh. “We asked ourselves whether brain imaging could turn up something concrete that differs between CFS patients’ and healthy people’s brains. And, interestingly, it did.”

The Stanford investigators compared brain images of 15 CFS patients chosen from the group Montoya has been following to those of 14 age- and sex-matched healthy volunteers with no history of fatigue or other conditions causing symptoms similar to those of CFS.

Three Key Findings

The analysis yielded three noteworthy results, the researchers said. First, an MRI showed that overall white-matter content of CFS patients’ brains, compared with that of healthy subjects’ brains, was reduced. The term “white matter” largely denotes the long, cablelike nerve tracts carrying signals among broadly dispersed concentrations of “gray matter.” The latter areas specialize in processing information, and the former in conveying the information from one part of the brain to another.

That finding wasn’t entirely unexpected, Zeineh said. CFS is thought to involve chronic inflammation, quite possibly as a protracted immunological response to an as-yet unspecified viral infection. Inflammation, meanwhile, is known to take a particular toll on white matter.

But a second finding was entirely unexpected. Using an advanced imaging technique — diffusion-tensor imaging, which is especially suited to assessing the integrity of white matter — Zeineh and his colleagues identified a consistent abnormality in a particular part of a nerve tract in the right hemisphere of CFS patients’ brains. This tract, which connects two parts of the brain called the frontal lobe and temporal lobe, is called the right arcuate fasciculus, and in CFS patients it assumed an abnormal appearance.

Furthermore, there was a fairly strong correlation between the degree of abnormality in a CFS patient’s right arcuate fasciculus and the severity of the patient’s condition, as assessed by performance on a standard psychometric test used to evaluate fatigue.

Right vs. Left

Although the right arcuate fasciculus’s function is still somewhat mysterious, its counterpart in the brain’s left hemisphere has been extensively explored. The left arcuate fasciculus connects two critical language areas of the left side of the brain termed Wernicke’s and Broca’s areas, which are gray-matter structures several centimeters apart. These two structures are important to understanding and generating speech, respectively. Right-handed people almost always have language organized in this fashion exclusively in the left side of the brain, but the precise side (left or right) and location of speech production and comprehension are not so clear-cut in left-handed people. (It’s sometimes said that every left-hander’s brain is a natural experiment.) So, pooling left- and right-handed people’s brain images can be misleading. And, sure enough, the finding of an abnormality in the right arcuate fasciculus, pronounced among right-handers, was murky until the two left-handed patients and four left-handed control subjects’ images were exempted from the analysis.

Bolstering these observations was the third finding: a thickening of the gray matter at the two areas of the brain connected by the right arcuate fasciculus in CFS patients, compared with controls. Its correspondence with the observed abnormality in the white matter joining them makes it unlikely that the two were chance findings, Zeineh said.

Although these results were quite robust, he said, they will need to be confirmed. “This study was a start,” he said. “It shows us where to look.” The Stanford scientists are in the planning stages of a substantially larger study.

 

Source: Stanford University Medical Center. “Brain abnormalities found in chronic fatigue patients.” ScienceDaily. ScienceDaily, 29 October 2014.  https://www.sciencedaily.com/releases/2014/10/141029084118.htm

 

Do anorexia, irritable bowel syndrome, chronic fatigues share a common cause?

Irritable bowel syndrome, chronic fatigue syndrome and anorexia nervosa may all have a common origin according to researchers.

They speculate that all three disorders may be caused by antibodies to the body’s own nerve cells because of a mistake by the immune system following infection.

At the moment, the ultimate cause of these illnesses remains a mystery.

Writing in Medical Hypotheses, Dr Jim Morris from the University Hospitals of Morecambe Bay NHS Trust, Dr Sue Broughton and Dr Quenton Wessels from Lancaster University say current explanations are unsatisfactory.

“Psychological factors might be important, but are unconvincing as the primary or major cause.

“There might, for instance, be an increased incidence of physical and sexual abuse in childhood in those who go on to manifest functional disorders. It is easy to see how this could influence symptoms in adults but it stretches credulity to imagine abuse as the sole and sufficient cause of the functional disorder.”

It is already well known that women are more at increased risk of autoimmune disease especially ones in which antibodies to the body’s own cells are thought to play a role, like thyroid disease, pernicious anemia and myasthenia gravis.

The researchers said: “The female to male ratio in these conditions is of the order of 10. The female excess in Irritable Bowel Syndrome, Chronic Fatigue Syndrome and Anorexia Nervosa is equally extreme and therefore this fits with the idea that auto-antibodies to nerve cells could be part of the pathogenesis of these conditions.”

The formation of auto-antibodies is found mostly among women and increases with age, which could be why these disorders are more common in midlife. Even with anorexia, which reaches a peak at the age of 30, auto-antibodies have been found in the bodies of patients.

There are also links with infection in that the onset of IBS commonly follows an episode of infectious diarrhea while chronic fatigue syndrome can be triggered by infectious mononucleosis and viral hepatitis.

Even anorexia could be influenced by secretions from bacteria affecting the brain, triggering the production of antibodies which affect mood and motivation.

“Auto-antibodies acting on the (brain’s) limbic system could induce extremes of emotion including disgust and fear. These then become linked, in the minds of adolescent girls, to culturally determined ideas of what is, and what is not, the ideal body shape and size. It is then a small step for disgust and fear to be directed to food and obesity which the fashion industry currently demonizes.”

If their idea is proven, the researchers suggest that these disorders may be amenable to treatment using pooled immunoglobulin from the blood of healthy people, especially in severe cases of anorexia where life is threatened. It should also be possible to identify and eliminate from the gut the bacteria which are triggering auto-antibodies.

Journal Reference: J.A. Morris, S.J. Broughton, Q. Wessels. Microbes, molecular mimicry and molecules of mood and motivation. Medical Hypotheses, 2016; 87: 40 DOI:10.1016/j.mehy.2015.12.011

 

Source: Lancaster University. “Do anorexia, irritable bowel syndrome, chronic fatigues share a common cause?.” ScienceDaily. ScienceDaily, 25 April 2016. https://www.sciencedaily.com/releases/2016/04/160425100204.htm

 

Vaccine-Related Chronic Fatigue Syndrome In An Individual Demonstrating Aluminium Overload

A team of scientists have investigated a case of vaccine-associated chronic fatigue syndrome (CFS) and macrophagic myofasciitis in an individual demonstrating aluminium overload.

This is the first report linking aluminium overload with either of the two conditions and the possibility is considered that the coincident aluminium overload contributed significantly to the severity of these conditions in a patient.

The team, led by Dr Chris Exley, of the Birchall Centre at Keele University in Staffordshire, UK, has found a possible mechanism whereby vaccination involving aluminium-containing adjuvants could trigger the cascade of immunological events that are associated with autoimmune conditions, including chronic fatigue syndrome and macrophagic myofasciitis.

The CFS in a 43-year-old man, with no history of previous illness, followed a course of five vaccinations, each of which included an aluminium-based adjuvant. The latter are extremely effective immunogens in their own right and so improve the immune response to whichever antigen is administered in their presence. While the course of vaccinations was cited by an industrial injuries tribunal as the cause of the CFS in the individual, it was not likely to be a cause of the elevated body burden of aluminium. The latter was probably ongoing at the time when the vaccinations were administered and it is proposed that the cause of the CFS in this individual was a heightened immune response, initially to the aluminium in each of the adjuvants and thereafter spreading to other significant body stores of aluminium.

The result was a severe and ongoing immune response to elevated body stores of aluminium, which was initiated by a course of five aluminium adjuvant-based vaccinations within a short period of time. There are strong precedents for delayed hypersensitivity to aluminium in children receiving vaccinations which include aluminium-based adjuvants, with as many as 1% of recipients showing such a response.

While the use of aluminium-based adjuvants may be safe, it is also possible that for a significant number of individuals they may represent a significant health risk, such as was found in this case. With this in mind the ongoing programme of mass vaccination of young women in the UK against the human papilloma virus (HPV) with a vaccine which uses an aluminium based adjuvant may not be without similar risks.

Recent press coverage of myalgic encephalomyelitis (ME) or chronic fatigue syndrome has highlighted the potentially debilitating nature of this disease and related conditions. The cause of CFS is unknown.

 

Source: Keele University. (2008, November 18). Vaccine-Related Chronic Fatigue Syndrome In An Individual Demonstrating Aluminium Overload. ScienceDaily. Retrieved March 4, 2017 from  https://www.sciencedaily.com/releases/2008/11/081118141856.htm

 

Chronic fatigue syndrome: The male disorder that became a female disorder

Previously long-term fatigue was considered a male disorder caused by societal pressures. Today women comprise the majority of ME patients, and they feel that their condition is their own fault.

Throughout history some people have suffered from a lack of energy and long-term, physical fatigue. Today these symptoms are classified as myalgic encephalomyelitis (ME) or chronic fatigue syndrome (CFS).

It is commonly thought that chronic fatigue has mainly psychological causes and that it affects perfectionistic women who cannot live up to their own unreasonably high standards.

This has not always been the case. Just over 100 years ago it was primarily upper class men in intellectual professions who were affected. “Neurasthenia,” as the condition was called at the time, was a physical diagnosis with high status.

No longer legitimate

“The medical understanding of long-term fatigue has changed. Previously the condition was viewed as a typically male disorder; now it is perceived as a typically female disorder. The diagnosis of neurasthenia, which has a male connotation, was changed to the ME diagnosis, which has a female connotation,” explains Olaug S. Lian, a sociologist and professor at UiT The Arctic University of Norway.

Together with Hilde Bondevik of the University of Oslo, Lian has studied how the view of women and perceptions of the body, gender and femininity in two different historical periods have been manifested in the medical understanding of long-term chronic fatigue.

“Long-term fatigue was viewed as a legitimate disorder, a result of the heroic efforts of the upper class male. Today, it is a stigmatizing disorder, understood as an expression of women’s lack of ability to cope with their lives, a kind of breach of character,” says Lian.

Not only has the fatigued patient changed gender. Previously doctors believed that long-term fatigue was a neurological, physical disorder, while today it is categorized primarily as psychological in nature. And while in the past, society was thought to be the cause of the disorder, today the individual is supposedly to blame.

What happened to cause this change?

Upper class diagnosis

At the end of the 1800s neurasthenia was the most widespread diagnosis for long-term fatigue. Neurologists believed the condition was caused by a physical, neurological disease that affected the entire body, causing intense, long-term fatigue.

Although women were also diagnosed with the disorder, the typical patient was a man, and not just any kind of man. He was “civilized, refined, and educated, rather than of the barbarous and low-born and untrained,” according to neurologist George Beard.

Society was to blame

Doctors at the time believed that the cause of the disorder could be found in a rapidly changing society — urbanization, industrialization and women’s entry into working life.

Quite simply, modern civilization ran roughshod over the nervous system of upper class men, who were overstimulated by too much pressure and activity and too little sleep and rest.

“It was regarded as both legitimate and understandable that even the ‘great men’ could fall apart as a result of long-term, difficult intellectual work. It was viewed as positive that the body sent signals when the burden was too great. The body was viewed as an electrical fuse box and the thinking was that it was better for one fuse to burn out rather than for the house to catch on fire,” says Lian.

Different genders, different causes

The comments about the diagnosis also revealed past understandings of biological gender differences. Women could get neurasthenia from sexual frustration, while men could get it from excessive sexual activity, including masturbation.

Moreover, there was a connection between gender and class.

“To simplify a bit, we can say that it was mainly middle class men and working class women whose diagnosis of neurasthenia was explained by overwork. For working class men it was due to sexual escapades, and for middle class women the cause given was heredity or ‘women’s issues’,” explains Lian.

The fall of neurasthenia

Neurasthenia lost its popularity as a diagnosis in the early 1900s. One reason for this was that psychiatry became a medical field in its own right.

“Psychiatry took neurasthenia with it and changed its definition from a physical to a psychological condition. Since women were regarded as psychologically weaker and therefore more disposed to mental illness, the disorder became a female problem,” says Lian.

Fight over definitions

Today ME is the most common name for the disorder, defined as long-term, intense fatigue that cannot be directly linked to a well-defined illness and that does not disappear with rest. The condition is chronic, it cannot be cured with medical treatment and there is disagreement as to the cause.

“The lack of scientifically generated findings, medical explanations and effective treatment make ME a diagnosis with low status and low legitimacy within the medical community,” says Lian.

Currently the main theory is that ME results from an inability to handle stress and that perfectionistic people — the “good girls” — are especially at risk. The debate about how ME should be understood and explained is highly polarized, between those who believe that it is an illness caused by infections or vaccination and those who believe that ME has mainly psychological causes.

“I would like to see some humility about what we actually know about the disorder and not present value judgments as facts. Doctors must also be honest and acknowledge that we have very little hard-and-fast knowledge about this condition,” states Lian.

Blame and shame

The two historical periods have almost identical depictions of the phenomenon of long-term fatigue, although the names are different. But there is one important difference: the disorder is no longer regarded as a legitimate, anticipated outcome of overwork.

“Today the medical community is searching for explanations of ME at the individual level. The ME patient is depicted as a woman with five-star goals and four-star abilities — with character traits that make it hard for them to cope with their own lives,” says Lian.

“When the entire problem is seen as the patient’s fault, the person experiences blame and shame because it is the patient, not society, who is the cause of the illness. It is therefore the individual who is responsible for coping with the illness, such as by changing her own thought patterns,” says Lian.

Wrong kind of tired

She points out that the ability to cope with one’s own life is an important value in Western culture. Mental disorders, however, are associated with weakness. The current understanding of long-term fatigue is also linked to how we think about tiredness, according to Lian.

“There are strong norms for when you are allowed to be tired and worn out and how you are supposed to show tiredness in daily life. If you have been awake all night with a sick infant, you have a good reason to be tired at work. Other reasons are less legitimate. Workplace reports of absence never state that someone is at the psychologist, while it is completely acceptable to say that someone is at the dentist.”

“Being tired for the wrong reasons is seen as a sign of weakness, which must be overcome and hidden. It is in this context that we must understand the medical theories on a lack of coping ability and the objections of ME patients to these theories,” says Lian.

She believes such norms often make ME patients feel that the psychological explanation is a burden, although doctors do not necessarily mean for it to have this affect.

“What is it about the ME debate that makes the opposing sides so obstinate?”

“The doctors and patients talk past each other. The doctors think that an ME diagnosis is value neutral, but the patient hears ‘it’s my fault that I am sick and it’s my responsible to get better’. But although most people feel that mental disorders have lower value than somatic disorders, it is not a given that the doctors do,” says Lian.

Gendered explanation disappeared?

Although about three of four people who are diagnosed with ME today are women, the explicit, biology-based gendered explanations have disappeared from the debate, according to Lian.

“This may simply be because today we put greater focus on gender equality — which makes it less legitimate to claim that women are naturally inferior to men,” says Lian.

However, she believes that the ME diagnosis embodies a view of women that has long historical roots.

“The profile of the upper class woman from the 1800s who cannot cope with pressure and stress both inside and outside the home is still with us today,” says Lian.

Cultural bias

“How can your analysis contribute to the current debate about ME?”

“We show how the medical understanding of fatigue and lack of energy is impacted by the norms and values of society at large, for example, that medical knowledge reflects the view of women in our culture. Norms and values combine with biomedical knowledge in a way that makes it difficult to see what is what,” says Lian.

 

Source: KILDEN – Information Centre for Gender Research in Norway. (2014, February 20). Chronic fatigue syndrome: The male disorder that became a female disorder. ScienceDaily. Retrieved March 4, 2017 from https://www.sciencedaily.com/releases/2014/02/140220083145.htm

 

Diagnosing Chronic Fatigue? Check For Sinusitis

Washington, D.C. – A new study published in the August 11 issue of the Archives of Internal Medicine demonstrates a possible link between unexplained chronic fatigue and sinusitis, two conditions previously not associated with each other. Also newly noted was a relationship between sinusitis and unexplained body pain. These findings offer new hope to patients lacking a diagnosis and treatment for fatigue and pain.

Sinus disease is seldom considered as a cause of unexplained chronic fatigue or pain, despite recent ear, nose, and throat (otolaryngology) studies documenting significant fatigue and pain in patients with sinusitis and dramatic improvement after sinus surgery. A Harvard study showed that fatigue and pain scores of sinusitis patients were similar or worse than a group 20 years older with congestive heart failure, lung disease, or back pain.

“Chronic fatigue is a condition that frustrates both doctors and their patients since treatments directed at just the symptoms without knowing the cause are typically ineffective,” said Alexander C. Chester, M.D., clinical professor of medicine at Georgetown University Medical Center and principal investigator of the pilot study. “While sinusitis will not be the answer for everyone who comes to an internist with unexplained fatigue or pain, this study does suggest that it should be considered as part of a patient’s medical evaluation.”

Through his private internal medicine practice, Chester questioned 297 patients, noting unexplained chronic fatigue in 22%, unexplained chronic pain in 11%, and both in 9%. While these numbers are consistent with previous studies, Chester observed an unusual connection between patients with chronic pain or fatigue: prevalent sinus symptoms. Sinus symptoms were nine times more common on average in patients with unexplained chronic fatigue than the control group, and six times more common in patients with unexplained chronic pain. In addition, sinus symptoms were more common in patients with unexplained fatigue than in patients with fatigue explained by a mental or physical illness, suggesting the syndrome of unexplained fatigue is more closely associated with sinusitis than are other types of fatigue.

The CDC approximates that sinusitis affects 32 million Americans. Rates are highest among women and people living in the South. Women comprised 46% of the participants in this study, but represented 60% of the group with fatigue, predominance also noted in most prior studies.

15 out of the 65 patients in Chester’s study met criteria for chronic fatigue syndrome (CFS), a severe form of unexplained chronic fatigue associated with body pains and other symptoms. Most CFS patients had sinus symptoms and many noted a sudden onset of their illness, similar to people with sinusitis.

“We clearly need to do more research to see if sinus treatments alleviate fatigue and pain. This study does, however, offer hope for possible help in the future.” said Chester.

Georgetown University Medical Center is an internationally recognized academic medical center with a three-part mission of research, teaching and patient care (through our partnership with MedStar Health). Our mission is carried out with a strong emphasis on public service and a dedication to the Catholic, Jesuit principle of cura personalis–or “care of the whole person.” The Medical Center includes the School of Medicine and the School of Nursing and Health Studies, both nationally ranked, and the world renowned Lombardi Cancer Center.

 

Source: Georgetown University Medical Center. (2003, August 14). Diagnosing Chronic Fatigue? Check For Sinusitis. ScienceDaily. Retrieved March 4, 2017 from  https://www.sciencedaily.com/releases/2003/08/030814072847.htm

Chronic fatigue syndrome patients had reduced activity in brain’s ‘reward center’

Chronic fatigue syndrome, a medical disorder characterized by extreme and ongoing fatigue with no other diagnosed cause, remains poorly understood despite decades of scientific study. Although researchers estimate that more than 1 million Americans are affected by this condition, the cause for chronic fatigue syndrome, a definitive way to diagnose it, and even its very existence remain in question. In a new study, researchers have found differing brain responses in people with this condition compared to healthy controls, suggesting an association between a biologic functional response and chronic fatigue syndrome.

The findings show that patients with chronic fatigue syndrome have decreased activation of an area of the brain known as the basal ganglia in response to reward. Additionally, the extent of this lowered activation was associated with each patient’s measured level of fatigue. The basal ganglia are at the base of the brain and are associated with a variety of functions, including motor activity and motivation. Diseases affecting basal ganglia are often associated with fatigue. These results shed more light on this mysterious condition, information that researchers hope may eventually lead to better treatments for chronic fatigue syndrome.

The study was conducted by Elizabeth R. Unger, James F. Jones, and Hao Tian of the Centers for Disease Control and Prevention (CDC), Andrew H. Miller and Daniel F. Drake of Emory University School of Medicine, and Giuseppe Pagnoni of the University of Modena and Reggio Emilia. An abstract of their study entitled, “Decreased Basal Ganglia Activation in Chronic Fatigue Syndrome Subjects is Associated with Increased Fatigue,” will be discussed at the meeting Experimental Biology 2012, being held April 21-25 at the San Diego Convention Center. The abstract is sponsored by the American Society for Investigative Pathology (ASIP), one of six scientific societies sponsoring the conference which last year attracted some 14,000 attendees.

More Fatigue, Less Activation

Dr. Unger says that she and her colleagues became curious about the role of the basal ganglia after previous studies by collaborators at Emory University showed that patients treated with interferon alpha, a common treatment for chronic hepatitis C and several other conditions, often experienced extreme fatigue. Further investigation into this phenomenon showed that basal ganglia activity decreased in patients who received this immune therapy. Since the fatigue induced by interferon alpha shares many characteristics with chronic fatigue syndrome, Unger and her colleagues decided to investigate whether the basal ganglia were also affected in this disorder.

The researchers recruited 18 patients with chronic fatigue syndrome, as well as 41 healthy volunteers with no symptoms of CFS. Each study participant underwent functional magnetic resonance imaging, a brain scan technique that measures activity in various parts of the brain by blood flow, while they played a simple card game meant to stimulate feelings of reward. The participants were each told that they’d win a small amount of money if they correctly guessed whether a preselected card was red or black. After making their choice, they were presented with the card while researchers measured blood flow to the basal ganglia during winning and losing hands.

The researchers showed that patients with chronic fatigue syndrome experienced significantly less change in basal ganglia blood flow between winning and losing than the healthy volunteers. When the researchers looked at scores for the Multidimensional Fatigue Inventory, a survey often used to document fatigue for chronic fatigue syndrome and various other conditions, they also found that the extent of a patient’s fatigue was tightly tied with the change in brain activity between winning and losing. Those with the most fatigue had the smallest change.

Results Suggest Role of Inflammation

Unger notes that the findings add to our understanding of biological factors that may play a role in chronic fatigue syndrome. “Many patients with chronic fatigue syndrome encounter a lot of skepticism about their illness,” she says. “They have difficulty getting their friends, colleagues, coworkers, and even some physicians to understand their illness. These results provide another clue into the biology of chronic fatigue syndrome.”

The study also suggests some areas of further research that could help scientists develop treatments for this condition in the future, she adds. Since the basal ganglia use the chemical dopamine as their major neurotransmitter, dopamine metabolism may play an important role in understanding and changing the course of this illness. Similarly, the difference in basal ganglia activation between the patients and healthy volunteers may be caused by inflammation, a factor now recognized as pivotal in a variety of conditions, ranging from heart disease to cancer.

Estimates from the CDC suggest that annual medical costs associated with chronic fatigue syndrome total about $14 billion in the United States. Annual losses to productivity because of lost work time range between $9 and $37 billion, with costs to individual households ranging between $8,000 and $20,000 per year.

 

Source: Federation of American Societies for Experimental Biology (FASEB). (2012, April 24). Chronic fatigue syndrome patients had reduced activity in brain’s ‘reward center’. ScienceDaily. Retrieved March 4, 2017 from https://www.sciencedaily.com/releases/2012/04/120424142109.htm

 

Visual stress could be a symptom of Chronic Fatigue Syndrome, research suggests

University of Leicester research team discovers vision-related abnormalities that could help in diagnosis of illness

People suffering from Chronic Fatigue Syndrome (CFS) could experience higher levels of visual stress than those without the condition, according to new research from the University of Leicester.

CFS, also known as Myalgic Encephalomyelitis (ME), is a condition that causes persistent exhaustion that affects everyday life and doesn’t go away with sleep or rest. Diagnosis of the condition is difficult as its symptoms are similar to other illnesses.

A research team from the University of Leicester led by Dr Claire Hutchinson from the Department of Neuroscience, Psychology and Behaviour has examined patients with and without CFS and has found that those suffering from the condition are more vulnerable to pattern-related visual stress, which causes discomfort and exhaustion when viewing repetitive striped patterns, such as when reading text.

The results of the study, which is published in the journal Perception, could help in the diagnosis of CFS, as the findings suggest that there are visual system abnormalities in people with ME/CFS that may represent an identifiable and easily measurable behavioural marker of the condition.

Dr Hutchinson explained: “Diagnosis of ME/CFS is controversial. With the exception of disabling fatigue, there are few definitive clinical features of the condition and its core symptoms, overlap with those often prevalent in other conditions. As a result, ME/CFS is often a diagnosis of exclusion, being made as a last resort and possibly after a patient has experienced a series of inappropriate treatments of misdiagnosed disorders.

“It is imperative therefore that research focuses on identifying significant clinical features of CFS/ME with a view to elucidating its underlying pathology and delineating it from other illnesses. Doing so will help researchers and healthcare professionals gain important insights into the condition, aid diagnosis and, in the longer term, inform evidence-based therapeutic interventions.”

The study assessed vulnerability of ME/CFS patients to pattern-related visual stress using a standardised test called the pattern glare test, in which people report the number of visual distortions they experience when looking at three repetitive striped patterns of different levels of detail.

During the study twenty patients with CFS and twenty patients without the condition were recruited.

Participants viewed 3 patterns, the spatial frequencies (SF) of which were either 0.3 (low-SF), 2.3 (mid-SF) and 9.4 (high-SF) cycles per degree (c/deg). They then reported the number of distortions they experienced when viewing each pattern.

Patients with ME/CFS reported more distortions on the intermediate striped pattern (Pattern 2) than people without the condition.

Dr Hutchinson added: “The existence of pattern-related visual stress in ME/CFS may represent an identifiable and easily measurable behavioural marker of ME. This could, in conjunction with other diagnostic tests, help delineate it from other conditions.”

The work was funded by ME Research UK who provided funding for a 1-year MPhil studentship, awarded to Rachel Wilson, who was supervised by Drs Claire Hutchinson and Kevin Paterson from the University of Leicester’s Department of Neuroscience, Psychology and Behaviour.

Dr Neil Abbot, Research & Operations Director at ME Research UK, added: “Around three-quarters of people with ME/CFS report a range of eye and vision-related symptoms that interfere with their everyday lives, yet there has been very little scientific investigation of the problem.

“Dr Claire Hutchinson and her team have previously confirmed the existence of eye movement difficulties in ME/CFS patients, and that symptoms, including eye pain, can be severe. Her new report in Perception extends these findings and raises the possibility that vision anomalies, including pattern-related visual stress, may have a diagnostic role in the disease.”

The study ‘Increased vulnerability to pattern-related visual stress in Myalgic Encephalomyelitis’ was published in the journal Perception.

Journal Reference: Rachel L. Wilson, Kevin B. Paterson and Claire V. Hutchinson. Increased Vulnerability to Pattern-Related Visual Stress in Myalgic Encephalomyelitis. Perception, November 2015 DOI: 10.1177/0301006615614467

 

Source: University of Leicester. (2015, November 24). Visual stress could be a symptom of Chronic Fatigue Syndrome, research suggests. ScienceDaily. Retrieved March 4, 2017 from https://www.sciencedaily.com/releases/2015/11/151124082235.htm