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Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating disorder with a worldwide prevalence of 0.2–0.5%. ME/CFS is characterised by severe disabling fatigue, exertional intolerance, sleep disturbance, muscle pain, orthostatic intolerance, and various other symptoms. Muscle weakness is a common symptom of ME/CFS, with patients experiencing a loss of muscle function and reduced endurance. This can make everyday activities, such as standing or combing hair, challenging. The causes of muscle weakness in ME/CFS are not fully understood but are believed to involve peripheral and central fatigue, biochemical abnormalities, and oxidative stress.
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What You'll Learn
Muscle pain and weakness
A study by Katrina Berne, PhD, reported a prevalence of 85–95% for muscle weakness in ME/CFS patients. Another study found that 84.3% of patients meeting the Fukuda criteria and 88.3% of patients meeting the Holmes criteria, in a cohort of 2073 CFS patients, reported muscle weakness.
The causes of muscle weakness in ME/CFS are not fully understood and are a topic of ongoing research. Some studies have found evidence of mitochondrial degeneration and biochemical abnormalities at the skeletal muscle level. Other studies have found that ME/CFS patients exhibit abnormal AMP-activated protein kinase (AMPK) activation and glucose uptake, as well as altered muscle membrane excitability.
Orthostatic intolerance is a common issue for people with ME/CFS, who may experience dizziness, altered vision, nausea, fatigue, headache, or sweating when standing still. This may be due to a lack of endurance in the muscles of the trunk, which maintain the upright position. A study by researchers at Antwerp University Hospital found that women with ME/CFS had significantly lower timed-loaded standing times than healthy women and women with osteoporosis.
A recent study on fruit flies and mice found that brain inflammation releases the IL-6 protein, which travels from the brain to the muscles and causes reduced energy production and function, resulting in muscle weakness. This study identified ways to block this process, which could have implications for treating or preventing muscle wasting in inflammatory diseases.
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Post-exertional malaise
The delayed onset of PEM, which can be from hours to days after the original trigger, is a characteristic that helps to distinguish ME/CFS from other fatiguing illnesses. This delay was noted by Yoshiuchi et al. in 2007, who wrote that "after a briefer maximal exercise task, reports of worsening CFS symptoms were inconsistent or absent until 5 days after the challenge, a pattern not typically observed in real life."
PEM is one of the four key symptoms necessary for a diagnosis of ME/CFS, as defined by the 2021 NICE Guideline on ME/CFS. The other three symptoms are:
- Debilitating fatigue that is worsened by activity and is not caused by excessive cognitive, physical, emotional, or social exertion.
- Unrefreshing sleep that does not provide restorative rest.
- Orthostatic intolerance, which means that symptoms worsen when upright (sitting, standing, or walking) and improve when reclined.
The underlying causes of PEM in ME/CFS are not yet fully understood, but research has identified various physiological abnormalities in patients with ME/CFS that may contribute to this symptom. For example, a study by Jammes et al. (2005) found a lengthened and accentuated oxidative stress response in ME/CFS patients after a cycling exercise until exhaustion. Other studies have reported abnormal skeletal muscle function, including mitochondrial degeneration and dysfunction in the Na+/K+-ATPase pump, which is responsible for regulating sodium and potassium levels in the body.
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Cognitive impairment
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating disorder of unknown origin, characterised by severe disabling fatigue. The cause of muscle weakness in ME/CFS is not fully understood, but it is believed to be a combination of peripheral and central fatigue.
ME/CFS patients experience muscle fatigability, where muscles become weaker after minor exertion, and full muscle power may take up to 5 days or longer to recover. This is often accompanied by muscle pain, cramps, twitching, and extreme tenderness. The severity of muscle weakness is proportional to the lowered physical performance of patients. A simple determination of maximal handgrip strength can be used to evaluate the limitation of physical performance.
There is evidence of a wide range of biochemical abnormalities at the skeletal muscle level in ME/CFS patients. Studies have found abnormal AMP-activated protein kinase (AMPK) activation and glucose uptake in ME/CFS patient skeletal muscles. Additionally, enhanced oxidative and nitrosative stress has been reported, with excessive production of reactive oxygen species (ROS) following physical exertion. This can lead to disrupted cell membrane function and damage to functional proteins and DNA.
Furthermore, ME/CFS patients often experience orthostatic intolerance, which includes symptoms such as dizziness, altered vision, nausea, fatigue, headaches, and sweating when standing still. This may be due to a lack of endurance in the muscles of the trunk, which are responsible for maintaining an upright position. Biomechanical weakness has been identified in the arms and trunk of women with ME/CFS, impacting their ability to perform everyday activities.
While the specific causes of muscle weakness in ME/CFS are still being investigated, current understanding points to a combination of peripheral and central fatigue, biochemical abnormalities, oxidative stress, and orthostatic intolerance. Further research is needed to improve the understanding and treatment of muscle weakness in ME/CFS patients.
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Orthostatic intolerance
OI is characterised by dizziness and lightheadedness, which can occur while recumbent or standing. In severe cases, patients may be unable to sit upright in bed. OI is often a sign of dysautonomia and can be classified into different types, including postural orthostatic tachycardia syndrome (POTS) and systemic exertion intolerance disease (SEID). SEID is a term used to describe ME/CFS while avoiding the stigma associated with the phrase "chronic fatigue syndrome" and emphasising the key characteristic of post-exertional malaise (PEM).
Published studies have proposed that deconditioning is a significant pathophysiological mechanism in various forms of OI, including POTS. However, conflicting opinions exist. Deconditioning can be objectively classified using predicted peak oxygen consumption (VO2) values from cardiopulmonary exercise testing (CPET). If deconditioning is a major contributor to OI symptoms, a correlation between the degree of reduction in peak VO2 during CPET and the degree of reduction in cerebral blood flow (CBF) during head-up tilt testing (HUT) would be expected.
Contrary to the deconditioning hypothesis, one study found that orthostatic intolerance in ME/CFS patients was not caused by deconditioning as defined by CPET results. Instead, an abnormally high decline in CBF during orthostatic stress was observed in all ME/CFS patients, regardless of their %peak VO2 results on CPET. This suggests that OI in ME/CFS may be related to autonomic dysfunction, neurological issues, and vestibular mechanisms rather than deconditioning.
To assess for orthostatic intolerance, Lucinda Bateman recommends the NASA 10-minute Lean Test, which is less taxing on the patient and can be administered in any physician's office.
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Sleep disturbances
The fatigue associated with ME/CFS is described as overwhelming and distinct from typical tiredness. It is characterised by a substantial drop in the ability to perform activities that were previously manageable, and it persists for six months or longer. This fatigue is often accompanied by orthostatic intolerance, where symptoms worsen when standing or sitting upright, leading to lightheadedness, dizziness, weakness, or fainting.
The impact of sleep disturbances in ME/CFS can be significant. The extreme tiredness and physical symptoms associated with the condition can make it challenging to carry out everyday tasks and activities. It may also affect their mental and emotional well-being, leading to low self-esteem and, in some cases, mental health concerns such as depression, stress, and anxiety.
Managing sleep disturbances in ME/CFS is crucial for improving overall well-being. Patients experiencing sleep issues may benefit from consulting a sleep specialist or considering specific medications to promote better sleep. Additionally, relaxation techniques such as meditation or yoga, and seeking support from family, friends, or support groups, can help address the mental and emotional aspects associated with the condition.
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Frequently asked questions
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex, multi-system, chronic illness that affects the brain and muscles, digestive, immune, and cardiac systems. It is classified as a neurological disorder by the World Health Organization.
The core symptom of ME/CFS is called post-exertional malaise (PEM), which is an increase in symptoms and reduction in function after minimal physical or mental activity. Other symptoms include muscle pain, sleep disturbance, orthostatic intolerance, and neurocognitive problems.
There is currently no specific diagnostic test for ME/CFS. Doctors diagnose it based on symptoms and by ruling out other conditions. The GP will ask about symptoms and medical history and may also perform blood and urine tests.
There is currently no cure for ME/CFS, but treatments such as exercise therapy, psychotherapy, dietary therapy, and probiotic uses may help manage the condition and relieve symptoms. Pacing and rest are also important self-management strategies.
The exact cause of muscle weakness in ME/CFS patients is not fully understood, but it is believed to be a combination of peripheral and central fatigue. Reduced central motor command to the muscles has been documented, and assessment of hand grip strength shows impaired strength and enhanced fatiguability.
