The Medical Mystery of Chronic Fatigue Syndrome
Myalgic encephalomyelitis/Chronic fatigue syndrome (ME/CFS) has long been dismissed as being a psychological condition. Due to a lack of understanding in the medical community, in the past it has taken people years to get an official diagnosis, if they get a diagnosis at all.
A 2015 report published by the Institute of Medicine (IOM) estimated that there between 836,000 and 2.5 million Americans suffering from ME/CFS, while a 2018 review estimated the rate to be higher—between 1.7 million and 3.38 million Americans. Worldwide, there could be as many as 17 to 24 million people with the condition. Sadly, most of these people have not been diagnosed. So in addition to their severe fatigue and other physical symptoms, they likely suffer from confusion, frustration, and a lack of sympathy and understanding from others.
The 2015 IOM report reviewed 9,112 published papers, and stated that ME/CFS is a serious physiological and not psychological illness. The report also criticized the lack of research funding, which has prevented progress in the understanding and treatment of the condition. While National Institutes of Health (NIH) funding for ME/CFS research has doubled in the past five years, advocacy groups stress the need for further increases in research funding because there are currently no FDA approved therapies for the condition.
Reports of full recovery from ME/CFS are rare; a review of 14 studies showed that just 5% of ME/CFS patients experience complete recovery from all symptoms. However, 39.5% of patients improve over time. Symptoms tend to be most severe in the first one to two years, and continued deterioration is not common.
If you suffer from ME/CFS, it’s important to know that the reason more people don’t recover is not because recovery isn’t possible—it’s because the condition is not well understood or treated. In this post I’ll discuss what most often causes the onset of ME/CFS, what research has discovered so far about the condition, treatments that have been studied, and how people report reducing their symptoms and recovering.
What is Myalgic encephalomyelitis/Chronic fatigue syndrome (ME/CFS)?
Myalgic encephalomyelitis means “muscle pain (myalgia) related to central nervous system inflammation (encephalomyelitis).” This name has been used since the 1950s, but in the past there has been debate about its accuracy since inflammation of the central nervous system had not been clearly demonstrated. In 1987, the Centers for Disease Control and Prevention (CDC) chose the name “chronic fatigue syndrome” as a more neutral and inclusive way to describe the condition. The 2015 IOM report proposed that the illness be renamed “systemic exertion intolerance disease (SEID)”, but many patients are not in favor of this new name.
People with ME/CFS typically have severe, unexplained fatigue that is not relieved with rest or sleep. ME/CFS sufferers often must decrease their work and daily activities substantially due to their fatigue. The condition can range in severity, and symptoms can fluctuate in severity from day to day. Some people describe it as being like having the worst flu you’ve ever had—all the time.
In addition to fatigue, other common symptoms include:
- Post-Exertional Malaise (PEM): extreme exhaustion, pain, feeling sick, and other symptoms that present after exercise or strenuous activity, often not starting until the next day
- Unrefreshing sleep
- Impaired concentration or short-term memory
- Muscle and joint pain
- Sore throat
- Tender or enlarged lymph nodes (swollen glands) in the neck or underarm area
- Gastrointestinal issues
If you think you have ME/CFS, your doctor may use the criteria proposed by the Institute of Medicine (IOM) to give you a formal diagnosis.
It’s important to be aware that other health conditions can cause symptoms similar to ME/CFS. Before diagnosing ME/CFS, your doctor will likely run tests to rule out:
- Adrenal insufficiency
- Heart disorders
- Sleep apnea or narcolepsy
- Hepatitis B or hepatitis C
- Major depression, bipolar disorder, and other psychiatric disorders
- Anorexia nervosa and bulimia
- Drug and alcohol abuse
Immune system dysregulation, a diagnostic biomarker, and neuroinflammation
An exact cause of ME/CFS has not been identified—likely because there is not just one cause. Different factors may contribute to the onset of the condition in different people. About 70% of cases are preceded by a virus, but it is clear that no single virus is the cause of ME/CFS. Some viruses that are known to lead to the condition are Epstein-Barr virus (EBV), cytomegalovirus (CMV), varicella-zoster virus (VZV), human herpesvirus (HHV-6, HHV-7, HHV-8), human parvovirus B19 (B19V), and enteroviruses. Bacterial infections and toxin exposure can also trigger the condition.
There have been dozens of reported outbreaks of ME/CFS, most of which followed viral outbreaks, and some of which occurred due to toxin exposure.
Since the most obvious clue to the cause of ME/CFS is that it tends to occur following viral infection, research has focused on the immune system’s role in the condition. A 2017 study found that levels of 17 cytokines (signaling proteins released by the immune system) correlated with severity of ME/CFS symptoms. These results established “a strong immune system component of the disease.” Other research has shown impaired function of natural killer (NK) cells, increased numbers of activated cytotoxic T cells, and the presence of various autoantibodies in people with ME/CFS.
In 2019, researchers at Stanford University School of Medicine developed a nanoelectrics blood-based test that, in the first phase of trials, accurately detected chronic fatigue syndrome 100% of the time. This is the first test to consistently detect a diagnostic biomarker for ME/CFS.
The test sends an electrical current through a blood sample. The immune cells and plasma of the blood interfere with the current, changing its flow, and these changes are monitored. The changes in electrical activity are directly related to the health of the blood sample. In the test, blood samples are “stressed” using salt, and then researchers compare how the blood samples respond to the stress. Immune cells and plasma of people with ME/CFS respond poorly to the stress, incapable of processing it properly, in stark contrast to the cells and plasma of healthy controls. The researchers are very hopeful that their findings will lead to more consistent diagnosis of the condition, as well as drugs being approved for the its treatment.
A 2018 article in the International Journal of Immunopathology and Pharmacology describes how ME/CFS is a complex, multi-system condition resulting from neuroinflammation. The researchers present a compelling case for the role of the hypothalamic paraventricular nucleus (PVN), a part of the brain responsible for absorbing and processing incoming stress signals.
Physiological stressors including viral infections, toxin exposure, and emotional trauma can cause dysfunction in the neural circuitry of the hypothalamic PVN. In Figure 2 below, the researchers list a wide range of stimuli—including exercise, emotional stress, sleep deprivation, viral infection, vaccinations, and toxin exposure—that all trigger the stress response, which includes inflammation. If the hypothalamic PVN was affected by neuroinflammation, it could explain the hypersensitivity of ME/CFS patients to various stressors, as well as account for their wide range of symptoms.
While it’s clear that a dysregulated immune response is present in the condition, the nervous system, endocrine system, and metabolic processes are involved as well. And recent research involving RNA sequencing shows how stress and inflammation pathways affect circadian rhythms, metabolic function, inflammation, cellular stress responses, and mitochondrial function in ME/CFS patients. With so many functions of the brain and body involved, and a range of factors that contribute to the condition, it’s no stretch to say that ME/CFS is a medical mystery.
What makes people susceptible to ME/CFS?
There are no clear answers to this question, at least not yet. It seems likely that several factors are present before initial onset, working together to make someone susceptible to developing the condition.
Recurrent infections weaken the immune system and increase risk of ME/CFS, as do immune deficiency and autoimmune conditions. Exposure to toxins and genetic predisposition also increase risk of developing the condition.
Another risk factor is stress, which makes sense—plentiful research shows how stress weakens the immune system. Stressful life events are often associated with the onset of ME/CFS. Experiencing chronic stress in daily life as well as having experienced childhood trauma both increase the chances of developing the condition.
Dysbiosis of the gut microbiome may increase risk of developing ME/CFS, or may be a symptom of the condition, or both. Gastrointestinal (GI) disturbances are common in ME/CFS, and reduced diversity of gut bacteria and altered composition of the gut microbiome are found in many people who suffer from the condition. A 2016 study showed that the GI tract of many ME/CFS patients is a pro-inflammatory environment. The researchers found that they were able to correctly identify people with ME/CFS nearly 83% of the time by comparing their gut microbiota to that of healthy controls. The researchers suggest that gut dysbiosis may contribute to ME/CFS symptoms and increase their severity.
Are there any successful treatments for ME/CFS?
There are no treatments for ME/CFS that have been approved by the FDA.
Initial trials of the antiviral drug rituximab, which wipes out most of the body’s B-cells (white blood cells that make antibodies) seemed promising. Unfortunately, further research showed no significant improvement of ME/CFS symptoms, and the drug can also cause serious adverse effects.
Studies of the antiviral drug valganciclovir published in 2012 and 2013 showed some improvements among ME/CFS patients who had elevated human herpesvirus 6 (HHV-6) and Epstein-Barr virus (EBV) IgG antibody titers. However, researchers note the need for longer treatment duration and a larger sample size in future studies of the drug.
In 2011, researchers in the U.K. followed 641 ME/CFS patients for a year and compared the effects of specialist medical care (SMC), graded exercise therapy (GET), cognitive behavioral therapy (CBT), and adaptive pacing therapy (APT). It was the largest ME/CFS study to date, and when it showed positive results, there was enthusiasm about the possible benefits of GET and CBT. Unfortunately, it came out that there were many flaws in the study. Patients, advocates, and other experts have since spoken out angrily about the misleading study results.
Knowing the role of immune system dysregulation and the presence of gut dysbiosis in ME/CFS, it may come as no surprise that fecal transplants are being used to treat the condition. That is, unless you’ve never heard of this procedure! Fecal transplantation, also called bacteriotherapy, is the transfer of stool from a healthy donor into the GI tract of another person. The procedure has been used in Chinese medicine for at least 1,700 years and is becoming increasingly mainstream. It is used in the U.S. to treat recurrent C. difficile colitis. In 2019, the first study of fecal transplantation for ME/CFS was published, with promising results.
How do people report reducing their symptoms and moving toward recovery?
In the absence of any approved medical treatment for ME/CFS, sufferers of the disease take their healing into their own hands. Many people who report improving their symptoms or recovering—like Bruce, Carrie, Kenneth, and Karen—describe how they used pacing to help them very gradually increase their activity levels and regain their health.
Pacing is basically what it sounds like: paying attention to your energy level and other symptoms, and only doing what you can do without making your symptoms worse. ME/CFS patients often find it helpful to have planned periods of rest throughout the day. It can take a great deal of willpower and discipline to modify your lifestyle in this way, sticking to what feels like a very limiting schedule. But the alternative—overdoing it and triggering the out-of-proportion intensification of symptoms (post-exertional malaise)—is worse.
An article in Frontiers in Physiology describes how fatigue serves a protective biological purpose: it arises in response to activity that is intense enough to threaten our homeostasis. When we feel fatigue, we slow down and rest in order to let the systems of our body recover. Thinking about fatigue in this way may be helpful for people who suffer with ME/CFS. The fatigue is a signal that your body needs to rest in order to maintain homeostasis and heal. If you can think of resting and pacing as being helpful, instead of limiting and frustrating, it can at the very least improve your state of mind, and likely aid in your improvement as well.
The focus on pacing as a method of recovery can make it sound like ME/CFS is a psychosomatic condition, but research has clearly shown that it is a physiological illness involving multiple systems of the body and causing many physical symptoms. The reason why pacing is helpful in recovery is simply because slowing down and paying attention to what your mind/body needs allows your systems to gradually heal and return to homeostasis.
Consider what happens when we come down with a virus: we feel tired, and we’re forced to take a few days off so that we can rest and allow our immune system to do its job. While ME/CFS is complex and extreme compared to this example, the principle of healing is the same. Our immune system wants to heal us and return the systems of our body to normal functioning, and often it can if we give it the chance. It is up to us to give it the very best possible chance to do its job. In addition to rest and pacing, this may involve stress reduction, changes in diet, taking supplements, spending time outdoors, meditation, and other lifestyle modifications that strengthen the immune system.
If you have reduced your symptoms or recovered from ME/CFS by any means and would like to share your story, I will add it to this post so that others can learn from your experiences. You can email me at [email protected]
Thank you to Anaya Smiley for sharing her story of full recovery from chronic fatigue syndrome:
“When I was diagnosed with Chronic Fatigue Syndrome (CFS)/Myalgic Encephalomyelitis (ME) two and a half years ago, the doctor told me surely the most famous of all CFS one-liners: “95% of people do not recover, so don’t get your hopes up.” My response internally was “Fuck that!” and externally “Well, I am one of the 5% and I will recover!” Click here to read Anaya’s full story.