ME/CFS is a very complex illness and it appears to have distinct subsets. It is clearly a biological illness, but it can be moderated somewhat by symptom management. A core issue in ME/CFS is massive energy depletion, that suggests that the mitochondria are not able to function properly, as they are the energy generating parts of cells. To be diagnosed with ME/CFS you must have post-exertional malaise and meet additional criteria.
Key characteristics of the disease:
- The inability to return to normal cellular energy production after an exercise challenge or stress test. (Snell et al 2013; Vermeulen et al 2010; Vanness et al 2011). This characteristic was the motivation behind the (failed) suggestion to rename ME/CFS as “Systemic Exercise Intolerance Disease” or SEID (more on the many names of ME/CFS below).
- Unrefreshing sleep. Many people with ME/CFS sleep too little or too much and all of it is typically not a restful as sleep should be. High alfa waves when they should be low and low delta waves when they should be high, may both relate to over-signalling in the brain and an over-active sympathetic system, that keeps the brain in a super-sensitive, unrejuvenated state.
- Immune dysregulation. People with ME/CFS often have abnormal response to fatigue and exertion that show up in recurring flu-like symptoms. Also significant subset of people with ME/CFS have unusually sensitive auto-immune type responses (Younger et al 2018).
Are ME and CFS one disease?
The most recent research emerging using metabolomic analysis suggests that soon we may be dividing Chronic Fatigue Syndrome into several subset diseases.
For example, as in Multiple Sclerosis, there is a relapsing-remitting group of people with ME/CFS which gets better and then worse. Another group in which things remain much the same for decades. Most severe are a progressive group where the illness gets worse, and whose metabolic profile shows many metabolites at barely survivable levels.
Stanford immunologist Mark Davis, and Canadian researchers see ME/CFS potentially as an autoimmune disease, having observed changes in patient T cells and B Cells and Natural Killer cells (NK Cells). In gene expression studies ME/CFS also resembles Systemic Inflammatory Response Syndrome (SIRS).
Jared Younger has been looking at subsets of people with fatigue and how their daily blood work tracks to immune and infection markers. He sees that about one in three ME/CFS patients have elevated C-reactive protein (CRP) levels that rise and fall in line with their fatigue. This suggests one third of ME/CFS patients may have an underlying infection.
Meanwhile, Myalgic Encephalomyelitis researcher, Canadian Byron Hyde, believes ME is most accurately described as always caused by enteroviruses, placing it within the family of polio diseases.
Does Chronic Fatigue Syndrome have another name?
Patients generally prefer to use the term Myalgic Encephalomyelitis as it conveys more medical credibility. Myalgic means muscle pain or tenderness. Encephalomyelitis means inflammation of the central nervous system. Chronic Fatigue Syndrome is rejected by patients for its lack of accuracy and gross misrepresentation of the illness, but it is more familiar to the general public. The name ME/CFS is an unsatisfactory solution until a better name can be agreed upon by the scientific and patient community. People who conform to the stricter ME diagnosis will use ME exclusively.
In Canada, the medical system naming protocol used by doctors and hospitals use a standardized code for disease names, call the ICD-10- CM. The name “Chronic Fatigue Syndrome” is coded as G93.3 in ICD-10-CM, where it is classified as “disease of the nervous system”. “Myalgic Encephalomyelitis” also uses the code G93.3.
Systemic Exercise Intolerance Disease (SEID) is a new name proposed by the committee that researched and proposed a new disease definition for ME/CFS, for the prestigious Institutes of Medicine. The name SEID has not taken hold, as it again fails to capture the full impact of the disease on other body systems, not just energy production.
Chronic Fatigue Immune Dysfunction (CFIDS), Post-Viral Fatigue Syndrome, febricula, Da Costa’s syndrome, neurasthenia, Chronic Mononucleosis, and Chronic Epstein Barr Virus are other names you’ll find with overlapping symptoms and diagnostic criteria. These names allude to common triggers in Canada such as mononucleosis (Epstein Barr Virus). There are several overlapping conditions such as persistent Lyme disease. There are differences between ME/CFS and Lyme reflected in the proteome of cerebral spinal fluid of patients.
How common is ME/CFS in Canada?
The 2015 Canadian Community Health Survey indicates 560,000 Canadians self-identify as having Chronic Fatigue Syndrome and/or Myalgic Encephalomyelitis, an alarming increase from 406,000 who reported the same a year prior. Clearly, this level of prevalence would make Canada one of the countries with the highest prevalence in the world. Given the self-reported nature of the study, these patients may represent an atypical, less severe group, as 60% considered themselves able to work outside the home. More typically, 13% of patients with ME/CFS are able to maintain full-time employment, and 25% or more are confined to their homes (housebound) or completely bedbound.
Roughly 2 women have ME/CFS for every man.
Is there a cure for ME/CFS?
Not yet, but they are emerging. Because there are subsets of ME/CFS, there are expected to be several treatments that will address the disease differently, based on the underlying metabolic and immune situation.
We are just beginning to see Canadian research and analysis that will translate into personalized medicine in other disease areas, such as cancer. To date, the Canadian Institutes of Health have been slow to provide research funding, providing only $600,000 since 2009. The grants are so rare, we can list them here:
The Canadian Institutes of Health Research is now investing in personalized medicine. The immediate example of how personalized medicine can benefit people in Canada will be the work being done by David Patrick’s team at UBC research to uncover an accurate immunosignature that will help determine those patients likely to respond to Rituximab. Rituximab is a chemotherapy currently used to cure B Cell Lymphoma currently undergoing a multi-site Phase III Clinical Trial in Norway to confirm early results that show a subset of people with ME/CFS respond well to the treatment.
As pharmaceutical treatments are still mostly in the proving stage, most statistics about ME/CFS reflect a history of neglect. Patients have explored supplements. Some people do go into remission and never relapse: about 6-10% of people with ME/CFS will get progressively better and back to normal (some longitudinal studies of adolescents suggest higher recovery rates). The accuracy of recovery rates is difficult, as they rely heavily on self-report. Self-perception is often an inaccurate measure of physical health, and can be influenced by psychological therapies. Most others have periods of good health interspersed with poor health. Post-exertional malaise persists for the vast majority but symptoms can be managed to some degree.
Simple “recovery stories” for ME/CFS should be looked at closely. Many patients have spent thousands of dollars on “cures”, to no effect. But there are subsets of ME/CFS that respond differently to treatments.
ME/CFS has suffered from a lack of research into biological treatments. There are emerging experimental treatments that address the underlying immune system dysfunction that characterizes ME/CFS, including rituximab and Ampligen. There is a Canadian campaign to provide Ampligen on a compassionate basis to Canadians with ME/CFS. In prior trials, Ampligen appears to have moved the dial on exercise tolerance (increased on average about 22%) and VO2 max (5.5%) and offered improvement to 30-40% of trial participants, with the strongest benefit experienced by those who had been sick between 2 and 8 years.
- Pacing. Don’t shoot the messenger – but it’s true, this frustratingly limiting practice is necessary for people with ME/CFS. Your cells are not working as they once did, you may have lost the ability to produce a core enzyme. ME/CFS is a relapsing and remitting illness which means that you will have good days and bad days; good months and bad months. This pattern is common with other autoimmune diseases. Pacing requires that you do not over-do it on good days. You must live within your new, smaller energy envelope. Even on good days, you must alter energy output with rest. Energy output includes mental effort, physical effort and stress. A crucial part of pacing is using a heart rate monitor.
- Treating SIBO – small intestinal bacterial overgrowth. Most people with ME/CFS at first experience bacterial overgrowth. It is treated with the antibiotic Rifaxin or herbal remedies
- Functional Medicine and Nutritional support. Many people with ME/CFS manage their symptoms by adopting dietary protocols such as the Wahls Protocol (12 cups of vegetables and dark fruit, no dairy, minimal grains, organic or wild protein sources); non-dairy; or a FODMAP diet. As there are subsets of patients, each must experiment with what works best for them. There are functional medicine practitioners in every major city in Canada who can help guide your choices.
- Vitamins. Many people with ME/CFS take:
- Magnesium. Take magnesium orally or as Epsom salt baths (1-2 cups per bath) if you find that you get loose stools from the pills.
- Vitamin D and often benefit from 5000 IU a day.
- Methylated B12 (methylcobalamin) and all B vitamins.
- Methylated Folate (Folic Acid is not the same thing)
- Vitamin C (1-3 G daily) and other anti-oxidants should be taken to assist with the excess of oxidation experienced by people with ME/CFS.
- Sleep medications and sleep hygiene. People with ME/CFS suffer from insomnia, sleep reversal or hypersomnia (too much). Establishing a consistent, calming sleep regime involves winding down and waking at a consistent time. When you wake, cue the pineal gland by exposing yourself to strong natural light. Getting sleep re-established may include taking sleep medications, or supplements such as melatonin.
- Treating POTS. Postural Orthostatic Tachycardia Syndrome (POTS) is a common co-morbidity. POTS is easy to diagnose and is very common among teens with ME/CFS. Treating symptoms POTS includes taking 2 salt tabs with a litre of water morning, and again late afternoon. Do this at least one hour before eating. Raise the head of the bed 6-8″, so that the entire bed it on a slant. Compression garments are helpful as well. For a range of tips, also see dysautonomia.
- Low blood volume may also be a contributor to anxiety-type symptoms, as adrenaline is required to contract the veins in the legs upon standing to maintain the blood volume in the upper body and brain. According to the Bateman Horne Centre, there is not enough volume to reach both body and brain when standing, so the “off” signal is not sent and excess adrenaline is released.
- Low Dose Naltrexone (LDN) is an emergent treatment that impacts both pain and microglia. It must be made by a compounding pharmacy. Typically, people with ME/CFS or fibromyalgia benefit from this low-risk treatment.
- Reducing stress and stimulation. People with ME/CFS are often experiencing the effects of adrenergic over-activation. Stresses you could tolerate before are now intolerable. With ME/CFS one may become very sensitive to light, sound and odours, all of which stimulate (or “fire up”) the nervous system. There are often genetic predispositions to this. There are several possible causes:
- Beta2 Adrenergic Receptor autoimmune attack. Treat with beta blockers
- Central Sensitization an over-active feedback loop between your brain’s primary “fight or flight” centre (the amygdala), your thoughts, your environment and your immune system.
- Some people with ME reject models such as Central Sensitization because of their reliance on bi-directional, mind-body feedback that can be misused by some physicians to imply ME/CFS is only a psychosocial illness. ME/CFS is a physiological illness.
- There does not seem to be sufficient parasympathetic response to calm down the over-active sympathetic system. Treatment with Diaphragmatic breathing helps some.
- For people with serious POTS and tachycardia (rapid heart rate), they may benefit from Beta Blockers such as Propranolol. Propranolol can also result in increased sleepiness and tiredness.
- Immune modulators also can be prescribed for ME/CFS, for those patients with low natural killer cell function. Rintatolimod treatment increases average NK cell activity over 100%. The drug Rintatolimod (Ampligen), while approved for use in Canada, can only be provided on a compassionate basis and it is very difficult to find a doctor able to pursue it on behalf of patients. Some physicians in Canada have prescribed Immunovir for immune dysregulation.
How much funding is provided to ME/CFS Research in Canada?
Eleven cents per patient. This is compared to $158 per patient with comparable illnesses such as Multiple Sclerosis or Parkinsons.
“ME/CFS is the lowest funded of any major disease. ME/CFS receives just 0.1% of the money that goes to HIV research.” Dr. Ron Davis, Stanford University.
How common is ME/CFS among Teenagers?
There is significant evidence from other countries that ME/CFS is increasingly common among teenagers. Using less stringent criteria than the Canadian Consensus Criteria for ME/CFS, the UK has started to track chronic fatigue through the Avon longitudinal “Children of the 90’s” study. In the UK, this study estimates that almost 2 per cent of 16-year-old girls have fatigue lasting more than six months. While chronic fatigue is not perfectly analogous to ME/CFS as they researchers do not ask about post-exertional malaise, just long-term fatigue, but it can be used as a potential indicator. A more rigorous Canadian evaluation is required. Currently, ME/CFS is under-diagnosed by physicians in teenagers, due to the problems with finding an appropriate specialist.
Is ME/CFS the same as Fibromyalgia?
No. Not quite but they are closely related. Fibromyalgia (FM) and ME/CFS are often experienced by the same people. When you have two illnesses at the same time this is called co-morbidity. American College of Rheumatology guidelines for diagnosing fibromyalgia has three criteria:
- Presence of other symptoms such as fatigue, waking up tired and trouble thinking
- No other underlying condition that might be causing the symptoms
- Widespread pain throughout your body for at least three months. “Widespread” is defined as pain on both sides of your body, as well as above and below your waist.
Underlying Cellular States of ME/CFS: Cell Danger Response Hypothesis
Cellular metabolism in ME/CFS is a poorly-researched field that is emerging as an exciting area for answers.
Mitochondrial specialist Robert Naviaux, believes that people with either ME/CFS may be experiencing a ‘cell danger response’ to triggers that prevents cells completing a healing cycle. The healing cycle is blocked or prolonged in ME/CFS. The evidence for this theory comes from observations of reduced metabolism in patients. It appears that for many, the body is continuing to fight infection or virus that is no longer present.
The chronic and complex state of change experienced in ME/CFS has been described as Cell Danger Response (CDR) by Bob Naviaux:
“CDR is a natural and universal cellular response to any injury or stress. Its purpose is to help protect the cell and to jump-start the healing process. But sometimes the CDR gets stuck. This prevents completion of the natural healing cycle and can permanently alter the way the cell responds to the world. When this happens, cells behave as if they are still injured or in imminent danger, even though the original cause of the injury or threat has passed. On a molecular level, the defended set points for cellular homeostasis are altered. This creates a pathological metabolic memory—an abnormal cellular response—that leads to chronic disease. When this happens during early child development, it causes autism and many other chronic childhood disorders. When it happens later in life, a persistent CDR can lead to immune exhaustion and it can lower the resistance to chronic infections. When it swings in the other direction, the immune system takes on a hair trigger and it leads to inflammatory and autoimmune disorders. In both cases, it increases the prevalence of chronic disease”