Medically, fatigue is a non-specific symptom, which means that it has many possible causes and accompanies many different conditions. Fatigue is considered a symptom, rather than a sign, because it is a subjective feeling reported by the patient, rather than an objective one that can be observed by others. Fatigue and 'feelings of fatigue' are often confused.
Physical fatigue, or muscle fatigue, is the temporary physical inability of a muscle to perform optimally. The onset of muscle fatigue during physical activity is gradual, and depends upon an individual's level of physical fitness, and also upon other factors, such as sleep deprivation and overall health. It can be reversed by rest. 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. The central component of fatigue is triggered by an increase of the level of serotonin in the central nervous system. During motor activity, serotonin released in synapses that contact motoneurons promotes muscle contraction. 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.
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.
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".
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. 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. 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.
Fatigue is generally considered a more long-term condition than sleepiness (somnolence). Although sleepiness can be a symptom of medical issues, it usually results from lack of restful sleep, or a lack of stimulation. 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. Both are often used interchangeably and even categorized under the description of 'being tired.' Oftentimes fatigue is described as an uncomfortable tiredness, whereas sleepiness is comfortable and inviting.