Definition and Overview
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a severe multisystem disease that causes significant functional impairment. The 1994 CDC (Centers for Disease Control and Prevention) criteria (Fukuda criteria) defined that unexplained fatigue lasting more than 6 months must be accompanied by 4 or more of 8 symptoms.
A 2015 report by the Institute of Medicine (IOM) proposed new diagnostic criteria (SEID criteria) and emphasized three core symptoms: extreme fatigue that impairs function (over 6 months), worsening symptoms after exercise (PEM), and non-restorative sleep. In addition, at least one of cognitive impairment or orthostatic intolerance is essential.
The global prevalence is estimated to be approximately 0.2-0.4%, and it occurs approximately 2-3 times more often in women than in men. The typical pattern is that adults with a high level of function before the onset of the disease rapidly decline in function after infection, surgery, or trauma.
Causes and Mechanisms
The pathophysiology of ME/CFS has not been fully elucidated, but multiple mechanisms are involved.
onset after infection
A significant proportion of all ME/CFS cases occur after infection. Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6), enterovirus, SARS-CoV-2, etc. are reported as triggering factors. After COVID-19, cases of Long COVID causing ME/CFS-like symptoms have increased rapidly.
Autonomic dysfunction
Decreased heart rate variability (HRV) and orthostatic intolerance are consistently identified in ME/CFS patients. There are reports that postural orthostatic tachycardia syndrome (POTS) occurs in approximately 25-50% of patients. Cognitive impairment and brain fog worsen due to decreased cerebral blood flow when standing up, which is linked to autonomic nervous system abnormalities.
Energy metabolism disorders
Abnormalities in mitochondrial function that generate cellular energy and changes in energy metabolism pathways are reported. In particular, metabolic patterns similar to the energy conservation state of dormant animals were discovered through metabolomics analysis in ME/CFS patients.
immune system abnormalities
Immune regulation abnormalities, such as decreased natural killer cell (NK cell) function, cytokine imbalance, and microscopic nerve inflammation, are reported. Microinflammation within the central nervous system contributes to neurological symptoms and cognitive decline.
symptoms
core symptoms
1. Post-exertional malaise (PEM)
PEM is the most characteristic symptom of ME/CFS. Fatigue, pain, and cognitive decline significantly worsen 24 to 72 hours after physical or cognitive activity, and can last for several days to weeks. Unlike general fatigue, it does not recover even with rest, and exercise actually worsens the symptoms.
2. non-restorative sleep
Even if you sleep enough hours, you still feel like you haven't slept at all. In polysomnography, abnormalities in sleep structure and decreased slow-wave sleep may be observed.
3. Cognitive decline (brain fog)
It is characterized by difficulty concentrating, short-term memory problems, difficulty finding words, and slow information processing speed. It is described as ‘feeling like being in a fog’ and is called ‘brain fog’.
4. Orthostatic intolerance
Dizziness, palpitations, headaches, and cognitive decline worsen when standing or sitting. POTS, orthostatic hypotension, and cerebral low blood flow are the causes.
accompanying symptoms
- muscle pain, joint pain
- Headache (tension or migraine pattern)
- Sore throat, tender lymph nodes around the neck
- Digestive symptoms such as irritable bowel syndrome
- Sensitivity to light and noise
- Sexual dysfunction, bladder irritability
diagnosis
Diagnostic criteria
There is no specific diagnostic test, so it is based on clinical criteria. First, exclude other organic causes (thyroid dysfunction, anemia, diabetes, sleep apnea, autoimmune disease, cancer, depression, etc.).
IOM (2015)/SEID criteria: 1. Fatigue that persists for more than 6 months and significantly impairs daily functioning 2. Symptom worsening after exercise (PEM) 3. non-restorative sleep 4. Cognitive impairment or orthostatic intolerance (either)
Autonomic function evaluation
The type and degree of autonomic dysfunction is evaluated through heart rate variability (HRV) analysis, tilt-table test, and active standing test. Measures heart rate, blood pressure response, and changes in cerebral blood flow when standing.
treatment
There is currently no cure for ME/CFS. The goal of treatment is to relieve symptoms and maintain function.
Energy Management (Pacing)
An energy envelope strategy to prevent PEM is key. Know your energy limits, keep your heart rate below your anaerobic threshold (AT), and regulate your activity level. Heart rate-based pacing using a heart rate monitor is utilized.
Progressive exercise therapy (GET) may worsen PEM and requires caution in ME/CFS. The 2021 NICE guidance in the UK withdraws its strong recommendation for GET.
Treatment of autonomic dysfunction
If POTS is present, increase fluid and salt intake, wear compression stockings, and use midodrine or pyridostigmine. Neuromodulation treatments such as stellate ganglion blockade and tDCS are used as an adjunct to restoring autonomic balance.
improved sleep
Sleep hygiene education and, if necessary, short-term sleep aid medications are used to improve non-restorative sleep.
symptomatic treatment
- Pain: low-dose naltrexone (LDN), low-dose antidepressants, nonsteroidal anti-inflammatory drugs (NSAIDs)
- Brain fog: Improving cerebral blood flow through treatment of orthostatic intolerance can sometimes alleviate cognitive symptoms.
- When accompanied by anxiety or depression: small doses of SSRI or SNRI
life guide
- Know your energy limits and work within those limits. Even on good days, don’t overdo it.
- Drink plenty of water (more than 2 liters per day) and maintain adequate salt intake.
- Maintain a regular sleep-wake rhythm, but limit naps to less than 30 minutes.
- Make stress management techniques (mindfulness, relaxation training) routine.
- Keep a symptom diary to identify activities and situations that worsen your symptoms.
- Regularly share your condition with your doctor and adjust your treatment plan.