When you first hear its name, the disease known as chronic fatigue syndrome may be hard to take seriously. After all, how bad could a little fatigue be? Aren’t all Northwestern students fatigued?
"We all know what it’s like to have run five miles and felt fatigued, or worked a hard week of work and feel fatigued by Friday,” said Carol Head, who developed chronic fatigue cyndrome in the '80s. "This is really fatigue such that cannot even be imagined .... Stepping out of your bed and walking to the bathroom – there’s no amount of willpower that could make you have the energy to do that."
Head is just one of the up to 2.5 million Americans who suffer from chronic fatigue, according to Institute of Medicine (IOM) estimates. While she now runs Solve ME/CFS Initiative, a Los Angeles-based advocacy group seeking to increase chronic fatigue research, Head knows all too well that both medical and public understanding of the disease remains low.
Yet thanks to an ongoing Northwestern study, doctors may soon learn what causes some types of chronic fatigue. The progress is slow and the obstacles are large. But one day, chronic fatigue patients may never be forced to deal with the paralyzing fatigue Head faces.
“I described the experience of it as a little death,” Head said. “The experience of recognizing that you may never be able to live the life you hoped to live.”
What is chronic fatigue syndrome?
Ben Katz, a professor in Pediatrics-Infectious Diseases at the Northwestern University Feinberg School of Medicine, has studied chronic fatigue syndrome since its explosion into the medical lexicon in 1984, when over 100 people in Lake Tahoe were diagnosed with persistent, severe fatigue. Doctors were dismissive, then perplexed. Blood tests were contradictory, brain scans inconclusive. The only clear evidence of disease was the disease itself: Patients were just too tired.
The apparent epidemic captivated the American public. The New York Times, Newsweek and Rolling Stone dubbed it names like “Yuppie Flu” and “Raggedy Ann Syndrome,” as experts noticed the symptoms sounded eerily like that of a disease called myalgic encephalomyelitis (ME). Realizing the two illnesses were the same, the Center for Disease Control and Prevention (CDC) published a case definition in 1988, naming it “chronic fatigue syndrome” for the first time. Today, it’s often popularly referred to as ME/CFS.
Doctors theorized that Epstein-Barr virus (EBV), the virus that causes mononucleosis or mono, led to ME/CFS, since chronic fatigue patients’ antibodies contained abnormalities sometimes found in mono patients. Katz, who happened to be studying EBV at a Yale University lab, co-wrote a paper pointing out that these abnormalities were also found in healthy people. He’s investigated the connections between EBV and ME/CFS ever since.
“EBV doesn’t cause chronic fatigue syndrome the same way that strep causes sore throats,” Katz said, “but certainly there are people who don’t recover from mononucleosis, and meet the criteria for chronic fatigue syndrome six months later.”
Today, in order to be diagnosed with ME/CFS, patients must feel severe fatigue for over six months prior to diagnosis, believe the disease “significantly interferes” with their daily life and possess four of eight symptoms in addition to the fatigue. The two most important symptoms are unrefreshing sleep and post-exertional malaise, or overwhelming exhaustion after minor activities.
After cooking dinner, one subject in a 2015 study conducted by scientists at the University of Alberta and the University of Calgary reported she could not stand. “My legs would just sort of be like rubber bands,” she said, “like I experienced after I had done this marathon 30-mile walk.” Another subject said that after overexertion, thinking was next to impossible: “I don’t recognize I have to pee. I don’t recognize our dog. I don’t recognize our house … I just stare.”
Six months after mono, 10 to 12 percent of adolescent patients have lingering symptoms and meet the requirements for a ME/CFS diagnosis, according to a 2009 study Katz co-authored and published in Pediatrics. One year after mono, seven percent still have not recovered. After two years, four percent.
Less than 10 percent of adults diagnosed with ME/CFS ever significantly recover, according to the University of Alberta and University of Calgary study.
Why does Northwestern’s study matter?
Katz’s 2009 study included over 300 teenagers diagnosed with mono in the Chicago area, but researchers could not conclusively find any ME/CFS biomarkers. (Biomarkers, which are physical proof of some kind of biological condition, can consist of anything from genetic mutations to glucose levels.) The only clue to identifying who would develop ME/CFS came from a survey, given to patients about two months after contracting mono, which asked about symptoms like lightheadedness, dizziness and blood pressure. Future ME/CFS patients consistently reported more of these symptoms than people who would later recover.
“Do you get bad mono and that’s why you develop chronic fatigue?” Katz asked. “Or is it something that predisposes you to get bad mono, even before you’re sick, and when you get EBV … you’re more likely to get chronic fatigue?”
Katz’s research indicates the latter. To prove it, he needs prospective data on healthy patients, from before they ever catch mono. Which is where his ongoing study on 6,000 Northwestern undergraduate students enters the picture. The study’s goal, Katz said, is to find out who might have a predisposition towards ME/CFS before contracting the disease.“If you run the numbers, a couple hundred [Northwestern student patients], between 300 and 600, will develop mono. And about 10 or 12 percent of them – between 50 and 70 – won’t recover,” Katz explained. “And if you can compare those who don’t recover to those who do recover, and you look at pre-illness data, and if you can find something that would be predictive, that would be incredibly exciting."
“Every study that has been conducted in this field has been based off of students who already developed mono,” said Yolanda Williams, the study’s project director. “We’re starting at a baseline healthy status, and that’s something that has never been done before.”
Why haven’t we solved chronic fatigue?
Williams works at the Center for Community Research, a DePaul University research lab run by Leonard Jason, DePaul professor of psychology and the study’s principal investigator alongside Katz. The walls of his spotlessly clean Chicago office are covered in awards and degrees, the silent evidence of his status as a pioneer in the ME/CFS field.
Jason started studying chronic fatigue after he caught mono and then ME/CFS in 1989, and had to leave his university job for over a year. When he recovered enough to return to work, he took a look at the ME/CFS literature.
“What I found was that the illness had a lousy name, chronic fatigue syndrome,” he recalled. “It had an even worse case definition. The tests used to assess people’s psychological conditions were inappropriate. The treatments being used were inappropriate. And the prevalence data was not very good. So I said to myself, ‘Boy, I’m gonna have business for the next 20 years.’”
But there’s so much that’s still unknown. Mono-related chronic fatigue is just the tip of the ME/CFS iceberg. Due to the variety of physiological responses and the small yet significant differences in patient symptoms, Jason thinks ME/CFS may actually be a collection of different disorders.
Those differences have yet to be truly studied, thanks in part to the lack of funding for research. Since the 2011 fiscal year, the National Institutes of Health (NIH) has only spent between $5 and $6 million annually on ME/CFS research.
Luckily, universities have a unique interest in understanding mono: keeping kids in school and not on medical leave.
“When we first approached Northwestern to do this [study], I was shocked at how anxious they were to help, because they lose kids all the time to mono,” Katz said. “That’s a big problem for colleges.”
What lies ahead?
In February, the Institute of Medicine (IOM) published a report on the ME/CFS field – or, as the IOM would now like it to be called, the Systemic Exertion Intolerance Disease (SEID) field.
Head says this name change gives her hope. It recognizes the frustration many patients feel when forced to call their illness chronic fatigue, which she sees as a trivializing name that fails to capture the disease’s severity.
“Chronic fatigue syndrome defines a symptom,” Head said. “No one calls lung cancer chronic coughing syndrome.”
Not so fast, Katz cautioned. He prefers the word “syndrome” because it means doctors use a constellation of symptoms to diagnose a disease, instead of a single definitive lab test. “It is what it is, and calling it something different doesn’t make people suffer any less or any more,” he pointed out.
Along with providing a new name and diagnostic criteria, the report calls for more research and training on ME/CFS. Katz and Jason’s study may just be the one of many new studies to come.