Fatigue is a subjective feeling of tiredness. It may be sudden or gradual in onset. It is a normal phenomenon if it follows prolonged physical or mental activity, and resolves completely with rest. It may be a symptom of one of many medical conditions if it prolonged, severe, progressive, or occurs without provocation. Physical Fatigue is the transient inability of muscles to maintain optimal physical performance, and is made more severe by intense physical exercise.[1][2][3] Mental Fatigue is a transient decrease in maximal cognitive performance resulting from prolonged periods of cognitive activity. Mental Fatigue can manifest as somnolence, lethargy, or directed attention Fatigue.[4] Fatigue and 'feelings of Fatigue' are sometimes confused.[5] Unlike weakness, Fatigue usually can be alleviated by periods of rest. 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. Fatigue can be reversed by rest.[6] 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.[7] The central component of Fatigue is triggered by an increase of the level of serotonin in the central nervous system.[8] During motor activity, serotonin released in synapses that contact motoneurons promotes muscle contraction.[9] During high level of motor activity, the amount of serotonin released increases and a spillover occurs. Serotonin binds to extrasynaptic receptors located on the axon initial segment of motoneurons with the result that nerve impulse initiation and thereby muscle contraction are inhibited.[10] 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.[11] 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".[12][13] 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.[4] It can manifest as somnolence, lethargy, or directed attention Fatigue. Decreased attention may also be described as a more or less decreased level of consciousness.[14] 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.[citation needed] The perception of mental Fatigue is believed to be modulated by the brain's reticular activating system (RAS).[citation needed] 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%.[15] Fatigue is a normal result of working, mental stress, overstimulation and understimulation, jet lag, active recreation, boredom, and lack of sleep. Medical 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. 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.[16] Chronic Fatigue is a symptom of many diseases and conditions. Some major categories of conditions that feature Fatigue include: 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.[17] Findings implicate neuroinflammation in the etiology of Fatigue in autoimmune and related disorders.[17] One study concluded about 50% of people who have Fatigue receive a diagnosis that could explain the Fatigue after a year with the condition. In those people who have a possible diagnosis, musculoskeletal (19.4%) and psychological problems (16.5%) are the most common. Definitive physical conditions were only found in 8.2% of cases.[21] If a person with Fatigue decides to seek medical advice, the overall goal is to identify and rule out any treatable conditions. This is done by considering the person's medical history, any other symptoms that are present, and evaluating of the qualities of the Fatigue itself. The affected person may be able to identify patterns to the Fatigue, such as being more tired at certain times of day, whether Fatigue increases throughout the day, and whether Fatigue is reduced after taking a nap. Because disrupted sleep is a significant contributor to Fatigue, a diagnostic evaluation considers the quality of sleep, the emotional state of the person, sleep pattern, and stress level. The amount of sleep, the hours that are set aside for sleep, and the number of times that a person awakens during the night are important. A sleep study may be ordered to rule out a sleep disorder. Depression and other psychological conditions can produce Fatigue, so people who report Fatigue are routinely screened for these conditions, along with drug abuse, poor diet, and lack of physical exercise, which paradoxically increases Fatigue. Basic medical tests may be performed to rule out common causes of Fatigue. These include blood tests to check for infection or anemia, a urinalysis to look for signs of liver disease or diabetes mellitus, and other tests to check for kidney and liver function, such as a comprehensive metabolic panel.[22] Other tests may be chosen depending on the patient's social history, such as an HIV test or pregnancy test. Fatigue is generally considered a more long-term condition than sleepiness (somnolence).[23] Although sleepiness can be a symptom of a medical condition, it usually results from lack of restful sleep, or a lack of stimulation.[24] 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.[25] 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).[26] Nevertheless such devices are not in common use outside Japan. Byung-Chul Han: Müdigkeitsgesellschaft. Matthes & Seitz, Berlin 2010, ISBN 978-3-88221-616-5. (Philosophical essay about Fatigue as a sociological problem and symptom).