Fatigue

Physical fatigue, or muscle fatigue, is the temporary physical inability of muscles to perform optimally. The onset of muscle fatigue during physical activity is gradual, and depends upon an individual's level of physical fitness – other factors include sleep deprivation and overall health.[11] Physical fatigue can be caused by a lack of energy in the muscle, by a decrease of the efficiency of the neuromuscular junction or by a reduction of the drive originating from the central nervous system, and can be reversed by rest.[12] The central component of fatigue is triggered by an increase of the level of serotonin in the central nervous system.[13] During motor activity, serotonin released in synapses that contact motor neurons promotes muscle contraction.[14] During high level of motor activity, the amount of serotonin released increases and a spillover occurs. Serotonin binds to extrasynaptic receptors located on the axonal initial segment of motor neurons with the result that nerve impulse initiation and thereby muscle contraction are inhibited.[15]

Muscle strength testing can be used to determine the presence of a neuromuscular disease, but cannot determine its cause. Additional testing, such as electromyography, can provide diagnostic information, but information gained from muscle strength testing alone is not enough to diagnose most neuromuscular disorders.[16]

People with multiple sclerosis experience a form of overwhelming lassitude or tiredness that can occur at any time of the day, for any duration, and that does not necessarily recur in a recognizable pattern for any given patient, referred to as "neurological fatigue", and often as "multiple sclerosis fatigue".[17][18]

Mental fatigue is a temporary inability to maintain optimal cognitive performance. The onset of mental fatigue during any cognitive activity is gradual, and depends upon an individual's cognitive ability, and also upon other factors, such as sleep deprivation and overall health. Mental fatigue has also been shown to decrease physical performance.[9] It can manifest as somnolence, lethargy, directed attention fatigue, or disengagement. Research also suggests that mental fatigue is closely linked to the concept of ego depletion. For example, one pre-registered study of 686 participants found that after exerting mental effort, people are likely to disengage and become less interested in exerting further effort.[19] Decreased attention can also be described as a more or less decreased level of consciousness.[20] In any case, this can be dangerous when performing tasks that require constant concentration, such as operating large vehicles. For instance, a person who is sufficiently somnolent may experience microsleep. However, objective cognitive testing can be used to differentiate the neurocognitive deficits of brain disease from those attributable to tiredness.

The perception of mental fatigue is believed to be modulated by the brain's reticular activating system (RAS).

Fatigue impacts a driver's reaction time, awareness of hazards around them and their attention. Drowsy drivers are three times more likely to be involved in a car crash and if they are awake over 20 hours, is the equivalent of driving with a blood-alcohol concentration level of 0.08%.[21]

In some areas it has been proposed that fatigue be separated into primary fatigue, caused directly by a disease process, and secondary fatigue, caused by more general impacts on the person of having the disease.[22][23][24][25]

Causes of acute fatigue include depression; chemical causes, such as dehydration, poisoning, low blood sugar, or mineral or vitamin deficiencies. Fatigue is different from drowsiness, where a patient feels that sleep is required.

Temporary fatigue is likely to be a minor illness like the common cold as one part of the sickness behavior response that happens when the immune system fights an infection.[26]

Prolonged fatigue is a self-reported, persistent (constant) fatigue lasting at least one month.

Chronic fatigue is a self-reported fatigue lasting at least six consecutive months. Chronic fatigue may be either persistent or relapsing.[27] Chronic fatigue is a symptom of many diseases and conditions. Some major categories of conditions that feature fatigue include:

• Autoimmune diseases,[28] such as celiac disease, lupus, multiple sclerosis,[29] myasthenia gravis, Sjögren's syndrome, and spondyloarthropathy
• Anxiety disorders such as generalized anxiety disorder[30]
• Blood disorders such as anemia and hemochromatosis
• Cancer, in which case it is called cancer fatigue
• Chronic fatigue syndrome (CFS)[31]
• Substance use disorders including alcohol use disorder[31]
• Depression and other mental disorders that feature depressed mood
• Developmental disorders such as autism spectrum disorder[32]
• Eating disorders, which can produce fatigue due to inadequate nutrition
• Endocrine diseases or metabolic disorders: diabetes mellitus, hypothyroidism and Addison’s disease[33]
• Fibromyalgia
• Gulf War syndrome
• Heart failure
• HIV
• Idiopathic chronic fatigue (ICF), which is chronic fatigue with no known cause that does not meet chronic fatigue syndrome criteria[34][35]
• Inborn errors of metabolism such as fructose malabsorption.[36][37]
• Infectious diseases such as infectious mononucleosis or tuberculosis[33]
• Irritable bowel syndrome
• Kidney diseases e.g. acute renal failure, chronic renal failure[33]
• Leukemia or lymphoma
• Liver failure or liver diseases e.g. Hepatitis[33]
• Lyme disease
• Neurological disorders such as narcolepsy, Parkinson's disease, Postural Orthostatic Tachycardia Syndrome and post-concussion syndrome
• Physical trauma and other pain-causing conditions, such as arthritis
• Sleep deprivation or sleep disorders, e.g. sleep apnea[33]
• Stroke
• Thyroid disease such as hypothyroidism

Fatigue may also be a side effect of certain medications (e.g., lithium salts, ciprofloxacin); beta blockers, which can induce exercise intolerance; and many cancer treatments, particularly chemotherapy and radiotherapy.

Inflammation has been linked to many types of fatigue.[28] Findings implicate neuroinflammation in the etiology of fatigue in autoimmune and related disorders.[28]

Fatigue is generally considered a more long-term condition than sleepiness (somnolence).[40] Although sleepiness can be a symptom of a medical condition, it usually results from lack of restful sleep, or a lack of stimulation.[41] Chronic fatigue, on the other hand, is a symptom of a greater medical problem in most cases. It manifests in mental or physical weariness and inability to complete tasks at normal performance.[42] Both are often used interchangeably and even categorized under the description of 'being tired.' Fatigue is often described as an uncomfortable tiredness, whereas sleepiness is comfortable and inviting.

Fatigue can be quantitatively measured. Devices to measure medical fatigue have been developed by Japanese companies, among them Nintendo (cancelled).[43] Nevertheless, such devices are not in common use outside Japan.