Monday, 25 March 2019

Chronotropic Intolerance: An Overlooked Determinant of Symptoms and Activity Limitation in Myalgic Encephalomyelitis / Chronic Fatigue Syndrome?

Todd E. Davenport 1,2*, Mary Lehnen 1, Staci R. Stevens 2, J. Mark VanNess 2,3, Jared Stevens 2 and Christopher R. Snell 2

1 Department of Physical Therapy, Thomas J. Long School of Pharmacy and Health Sciences, University of the Pacific, Stockton, CA, United States
2 Workwell Foundation, Ripon, CA, United States
3 Department of Health, Exercise, and Sport Sciences, College of the Pacific, University of the Pacific, Stockton, CA, United States

Post-exertional malaise (PEM) is the hallmark clinical feature of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). PEM involves a constellation of substantially disabling signs and symptoms that occur in response to physical, mental, emotional, and spiritual over-exertion. Because PEM occurs in response to over-exertion, physiological measurements obtained during standardized exertional paradigms hold promise to contribute greatly to our understanding of the cardiovascular, pulmonary, and metabolic states underlying PEM. In turn, information from standardized exertional paradigms can inform patho-etiologic studies and analeptic management strategies in people with ME/CFS. Several studies have been published that describe physiologic responses to exercise in people with ME/CFS, using maximal cardiopulmonary testing (CPET) as a standardized physiologic stressor. In both non-disabled people and people with a wide range of health conditions, the relationship between exercise heart rate (HR) and exercise workload during maximal CPET are repeatable and demonstrate a positive linear relationship. However, smaller or reduced increases in heart rate during CPET are consistently observed in ME/CFS. This blunted rise in heart rate is called chronotropic intolerance (CI). CI reflects an inability to appropriately increase cardiac output because of smaller than expected increases in heart rate. The purposes of this review are to (1) define CI and discuss its applications to clinical populations; (2) summarize existing data regarding heart rate responses to exercise obtained during maximal CPET in people with ME/CFS that have been published in the peer-reviewed literature through systematic review and meta-analysis; and (3) discuss how trends related to CI in ME/CFS observed in the literature should influence future patho-etiological research designs and clinical practice.

To read the full article, please go to -

Saturday, 16 March 2019

The Myth of “It’s All in Your Head” 

March 14, 2019

DePaul scientists work to unravel the mystery of chronic fatigue syndrome

By Abby Pickus

In 1980, a high school English teacher from Wisconsin named Pat Fero went on a trip to England. Healthy and in her 30s, she noticed something was very wrong toward the end of the trip.

“We were in this beautiful countryside, and we went to climb a hill to get a better view of a lake and I just couldn’t do it. I thought, I am really out of shape. I couldn’t get up that hill. My legs hurt, and I was dizzy and short of breath,” recalls Fero.

When she returned home the fever hit.

“I had a 104° fever for a week and a headache from hell. I had extreme pain in my neck and shoulders that lasted another week,” she says.

Over the next few years she got progressively sicker until she couldn’t climb the stairs at school without resting on the landing. Then she was unable to write on the chalkboard. “I would misspell things. I couldn’t form the letters correctly. I would miss words. Day-to-day communication became tough. That’s why I left the classroom. You can’t be in front of 20-some kids and seriously not know what you’re talking about,” she says.

In 1988, Fero went on medical leave—and never returned. That was the year she finally received a diagnosis for her suffering: chronic fatigue syndrome.

Mystery Disease

Tragically, Fero is not alone. Using research data developed at DePaul, the Centers for Disease Control and Prevention (CDC) estimates that there are currently more than 1 million people in the U.S. and more than 17 million worldwide with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME)—and these are just the ones who have been diagnosed. (See What’s in a Name?)

Often triggered by a virus, this debilitating disease continues to plague people for years with symptoms that run the gamut from nerve pain and cognitive impairments to a fatigue better characterized as bone-crushing exhaustion.

“Don’t use the word fatigue. It’s an exhaustion so severe that you can’t stand up because you feel like you’re going to faint,” says Fero.

Often lumped together with other so-called “mystery illnesses” such as Lyme disease and fibromyalgia, CFS/ME is historically misdiagnosed or underdiagnosed simply because one of its defining symptoms—fatigue—is both commonplace and seemingly benign. Adding insult to injury, CFS/ME is notoriously stigmatized because of its name “chronic fatigue,” suggesting that the patient is merely tired.

But the medical community is baffled, from what causes it to what it really is: A brain disease? A virus? And with federal funding for research into CFS/ME improving but still lower than for other major diseases, the quality of life for millions of Americans is left hanging in the balance.

Enter Leonard Jason, a professor of psychology at DePaul, who with his team has been making serious inroads into cracking the code on this mystery illness. “DePaul has been trying to validate the experience of patients with CFS/ME, to find ways to lessen the burden of this illness by reporting on accurate prevalence numbers among adults and children, to find effective treatments and to understand its etiology,” says Jason.

It’s a tall order, but with more than 800 professional publications and 25 books to his name (many on CFS/ME), plus more than $36 million in research grants, Jason and the DePaul Center for Community Research have emerged as leading figures in an area of medicine otherwise shrouded in darkness.

Center for Community Research

Jason has been at DePaul since 1975. Boyish and slender with round wire-framed glasses and a friendly manner, he arrived at DePaul immediately after receiving his PhD from the University of Rochester, having been drawn initially to DePaul because of its values. In fact, his area of psychology—clinical community psychology—has distinctly Vincentian roots with its emphasis on understanding and addressing social problems, particularly for the underserved. It was in this vein that Jason founded the Center for Community Research in 2001.

Jason’s initial interest in CFS/ME was personal. In 1989, he was hit with the disease after coming down with mononucleosis, which many researchers now feel could be one of the triggers for the illness. It took him a full year to feel better, and when he did, he started plowing through the meager literature on the disease. What he discovered was that he was in a unique position to make a difference.

“It just seemed like there were so many interesting issues with this illness and that I, as a person who had experienced it myself who was also a psychologist with a background in strong research methods, could spend a lot of time making contributions,” he says. He then pursued the matter from all angles, from correcting what he considered to be an inaccurate case definition to countering inappropriate CFS/ME myths from some in the medical community.

“It was evident to me that there was a lot of stigma against people who had what’s called chronic fatigue syndrome, which is not a very good term because it is trivializing,” he says. Also trivializing were the treatments recommended to patients. “Here you have these exhausted and sick people, and you basically want them to do exercise and be more active because that’s what you thought would help them,” he says.

It was Jason’s team who coined the term “staying within the energy envelope” as a counter to these popular treatments. In numerous papers, Jason showed that for patients with CFS/ME, pushing too hard leads to serious consequences known among ME sufferers as post-exertional malaise, where the body and brain shut down.

One of Jason’s most significant contributions to the field has been quantifying the number of adults in the U.S. with the disease. “The prevalence rates were not very accurate back in the ’90s when I first started doing research, and the methodology used by the CDC was flawed. At the time, it was considered a rare ‘Yuppie flu’ disease primarily affecting white middle-class women. As a result of this myth, the federal government did not provide a lot of resources for those people who had this illness,” he says.

Throughout the 1990s, Jason and his team conducted a community-based epidemiology prevalence study and came to a staggering conclusion: Instead of 20,000 Americans with this illness, the number was probably closer to a million, and it was actually minorities, particularly Hispanics, who were disproportionately affected by the disease. The CDC has since updated its figures based on DePaul’s research and its own subsequent study.

While serving on the CDC’s Chronic Fatigue Syndrome Advisory Committee in the mid-2000s, Jason was able to make recommendations to the Secretary of U.S. Health and Human Services about the research and service needs of this patient group.

Mapping Brainwaves

One sunny, summer afternoon, research scientists Marcie and Mark Zinn were hard at work in the laboratory they fashioned inside DePaul’s Center for Community Research to view images created by quantitative electroencephalography (qEEG) that maps the brain waves of people with CFS/ME. Pointing to two computer monitors displaying a 3D cross section of the brain alongside the EEG squiggles tracking the brain’s metabolic activity, Marcie shows how the technology uses low-resolution electromagnetic tomography (LORETA) software to estimate the sources in the brain causing its dysregulation. It does this all at the millisecond level, the time frame in which the brain actually operates—a vast improvement over the functional MRI, which has a 2- to 3-second delay.

“A normally functioning brain depends on the neurons functioning within a certain time frame. For patients with ME, the neurons are either damaged or dead, which causes cognitive impairments because of the slowed speed and the first part of the processing hasn’t been resolved before they move on to the next,” says Marcie.

qEEG was developed by Clinical Neuroscience Professor Robert Thatcher, who uses it to examine all types of brain injuries; it is also used to study the brains of those with autism and traumatic brain injury. DePaul is the only research center in the world using qEEG to link communication between neural networks and the cognitive dysregulation of patients with CFS/ME. is is something the Zinns hope will change.

“Right now it’s very hard to measure ME, which makes it hard to diagnose. People either have to go to an infectious diseases doctor or [we] have to wait until they’re dead for their brains to be autopsied.

“One of the things we’re trying to work on is for doctors to use our technology in their offices to help potential patients with ME,” says Marcie, adding that the diagnostic procedures used currently are only accurate in about 50 percent of the cases.

The Zinns began using qEEG in 2001 to study the brain patterns of concert pianists, a profession they both pursued before switching to careers in psychology. They transitioned to studying patients with CFS/ME in 2010 at Stanford University under Jose Montoya, an infectious disease doctor, and have continued their work since joining DePaul in 2015. Marcie is the former director of the center’s cognitive systems neuroscience unit, and Mark is pursuing a PhD in community psychology.

They have studied the brains of more than 200 patients with ME/CFS and have published many research articles on different aspects of the disease. Among their discoveries is that post-exertional malaise is truly all in patients’ heads—just not in the way doctors thought.

“Their brain function literally tanks. We can actually see that,” says Marcie. They’ve also seen how CFS/ME patients’ everyday waking brain is drowsy because of too many delta waves.

All these findings have given those suffering from the disease the kind of validation they have long sought. “To see your brain light up like a Christmas tree when you do a simple task really validates what I already know,” says Fero, who came to DePaul to participate in the studies. “I didn’t think I wasn’t able to write on the chalkboard because there was some psychiatric problem. I knew there was something wrong with my brain. These 3D scans confirm that.”

For Marcie, who also suffers from the disease, focusing on the brain is a significant step in the right direction particularly because blood tests cannot detect CFS/ME. “Just because a doctor doesn’t find any indicators of illness in a person’s blood doesn’t mean they aren’t sick. It just means they aren’t looking where the problem is,” says Marcie.

The Invisible Demographic

“I really don’t want to die, but it’s really hard to call this living,” says CFS/ME patient Jennifer Brea in her chilling documentary, “Unrest,” which documents just how widespread—and debilitating—the disease is. Some of the most heart-wrenching stories in the film are about young people who have spent most of their formative years bedridden.

It turns out that children are the most invisible demographic to be hit by CFS/ME. Only Jason and his team are putting a number on this phenomenon. They are currently wrapping up a rigorous study of 10,000 children to estimate its prevalence among youth.

“Sometimes there are children who are functioning at a very high level and then all of a sudden something happens—there’s an accident or there might be some type of virus, we’re still trying to understand that—and then their functioning goes down considerably. Their parents and school officials often think, ‘Is this child just malingering?’ Unless there is an ally to help the child, the child could easily get stigmatized for this condition,” says Jason.

In another prospective longitudinal study, Ben Katz, a professor of pediatrics at Northwestern’s Feinberg School of Medicine, is partnering with Jason to look at the link between mononucleosis, which is triggered by the Epstein-Barr virus, and CFS/ME in youth. The study looks at which percentage of those who develop mono will go on to develop CFS/ME and why. “About 5 percent of all kids who go to college will get mono before they graduate, and about 12 percent who get mono will meet criteria for CFS/ME six months later,” says Katz. “Why do most people recover? Nobody knows the answer, and that’s why we decided to study college kids. By enrolling people when they’re healthy, you can see if they get mono and why some recover and some don’t.”

Data collection to estimate the prevalence of CFS/ME among youth will be completed in 2019, and soon after, papers will be submitted for publication, according to Jason. The results of the mono-CFS/ME study will also be released in 2019.

“This is an exciting study as we are getting close to finding out some kind of answers,” adds Katz.

On the Brink of a Breakthrough

Answers are exactly what people like Fero need. “I am almost 69, and I’ve had this for more than half my life,” she says. She’s buoyed, however, by a changing tide of events, from an emboldened sense of advocacy among patients through the power of social media to the growing number of institutions working to find some answers. Stanford University, for example, has created both an initiative to study CFS/ME and a CFS research center under the direction of Ronald Davis, a professor of biochemistry and genetics whose son has a severe case of the disease.

“Are we getting closer to a breakthrough?” Jason asks. “I think so, yes.”

Saturday, 9 March 2019

Looking back with ME on Amazon Kindle

I am pleased to say that my little book “Looking back with ME” is now available as an Amazon kindle book – click here. (It is available on the Kindle Unlimited scheme, for anyone who subscribes to it.) Many people with ME (myself included) find it easier to read books on a kindle rather than the printed variety, so I am hoping that having the book for Amazon kindle might be a help to some. (Just in case anyone is wondering, I don’t make any money from either the printed or e-book versions.)

Monday, 4 March 2019

My grace is sufficient for thee

C H Spurgeon's Morning Devotional for 4th March

"My grace is sufficient for thee."

2 Corinthians 12:9

If none of God's saints were poor and tried, we should not know half so well the consolations of divine grace. When we find the wanderer who has not where to lay his head, who yet can say, "Still will I trust in the Lord," or when we see the pauper starving on bread and water, who still glories in Jesus; when we see the bereaved widow overwhelmed in affliction, and yet having faith in Christ, oh! what honour it reflects on the gospel. God's grace is illustrated and magnified in the poverty and trials of believers. Saints bear up under every discouragement, believing that all things work together for their good, and that out of apparent evils a real blessing shall ultimately spring-that their God will either work a deliverance for them speedily, or most assuredly support them in the trouble, as long as He is pleased to keep them in it. This patience of the saints proves the power of divine grace. There is a lighthouse out at sea: it is a calm night-I cannot tell whether the edifice is firm; the tempest must rage about it, and then I shall know whether it will stand. So with the Spirit's work: if it were not on many occasions surrounded with tempestuous waters, we should not know that it was true and strong; if the winds did not blow upon it, we should not know how firm and secure it was. The master-works of God are those men who stand in the midst of difficulties, stedfast, unmoveable,-

"Calm mid the bewildering cry,
Confident of victory."

He who would glorify his God must set his account upon meeting with many trials. No man can be illustrious before the Lord unless his conflicts be many. If then, yours be a much-tried path, rejoice in it, because you will the better show forth the all-sufficient grace of God. As for His failing you, never dream of it-hate the thought. The God who has been sufficient until now, should be trusted to the end.

Friday, 1 March 2019

Chronic Fatigue Syndrome: It’s Real, and We Can Do Better

Medscape/CDC: Chronic Fatigue Syndrome: It’s Real, and We Can Do Better | 26 February 2019

My name is Dr Elizabeth Unger and I am chief of CDC’s Chronic Viral Diseases Branch, which houses the myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) program.

An estimated 836,000 to 2.5 million Americans suffer from ME/CFS, a serious, long-term illness that can severely impair the ability of those affected to live normal lives. But the majority of those affected are not diagnosed, and many struggle with symptoms for years before receiving a diagnosis.

The absence of a definitive diagnostic test contributes to this problem. In addition, most medical schools in the United States do not include ME/CFS in their physician training.

Less than one third of medical school curricula and less than half of medical textbooks in the United States address ME/CFS, so many healthcare providers need more information about this condition.

When I meet with those living with ME/CFS and their loved ones, the overarching concern that I hear is the difficulty finding good healthcare from informed and compassionate providers.

To address this need, we released an updated CDC website about ME/CFS for healthcare providers in July 2018. The new site was designed specifically with clinicians in mind. It offers information about how clinicians can better assess and help their patients manage this illness.

The new content includes:

ME/CFS is a complex, chronic, debilitating illness with systemic effects. It’s characterized by reduced ability to perform activities that were well tolerated pre-illness, accompanied by profound fatigue not improved by rest, and lasting for more than 6 months.

A hallmark of ME/CFS is that symptoms can worsen after physical, mental, or emotional effort, a manifestation known as postexertional malaise. Patients with ME/CFS also have unrefreshing sleep.

Other common symptoms are orthostatic intolerance, cognitive impairment, and pain. As can be observed in people with other long-term chronic illnesses, secondary psychological symptoms such as depression and anxiety may also be present in some patients with ME/CFS.

ME/CFS is a biological illness, not a psychological disorder. Patients with ME/CFS are neither malingering nor seeking secondary gain. These patients have a variety of abnormalities that affect multiple systems, such as:

  • Immune and neuroendocrine;
  • Cellular metabolism; and
  • Autonomic system regulating blood pressure and heart rate.

A healthcare provider can make the diagnosis of ME/CFS based on a thorough medical history and physical examination, as well as a targeted workup with screening laboratory tests for other fatiguing illnesses.

While there are currently no diagnostic or confirmatory tests, or US Food and Drug Administration–approved drugs specifically for the treatment of ME/CFS, patients benefit from a thorough medical evaluation and good clinical care. Helping patients achieve relief from symptoms and improved quality of life are the main goals of treatment.

In working toward these goals, it’s important to prevent harm that can occur from triggering postexertional malaise. It’s also vital to acknowledge the clinical significance of the condition and to validate the experience and concerns of patients and their loved ones. This acknowledgement often brings patients and families a sense of support and strengthens trust between patients and providers.

It is important to emphasize that anyone can develop ME/CFS. While it is more common in women, and most common in people between 40 and 60 years of age, the illness affects children, adolescents, and adults of both sexes and all ages.

Besides information for healthcare providers, the updated ME/CFS website lists resources for families, patients, and schools, including patients’ personal accounts of living with ME/CFS, called Voice of the Patient.

We invite you to review the information on the website and hope that it will help ensure that clinicians like yourself are informed about how to recognize and manage this debilitating illness. You can provide timely diagnosis and appropriate care for patients with ME/CFS. Thank you.

Web Resources:

Public Information from the CDC and Medscape.