Central nervous system fatigue, or central fatigue, is a form of fatigue that is associated with changes in the synaptic concentration of neurotransmitters within the central nervous system (CNS; including the brain and spinal cord) which affects exercise performance and muscle function and cannot be explained by peripheral factors that affect muscle function. In healthy individuals, central fatigue can occur from prolonged exercise and is associated with neurochemical changes in the brain, primarily involving serotonin (5-HT), noradrenaline, and dopamine. Central fatigue plays an important role in endurance sports and also highlights the importance of proper nutrition in endurance athletes.

Patients with chronic orthostatic intolerance have symptoms on most or all days. Their symptoms may include most of the symptoms of acute OI, plus:

- Nausea

- Neurocognitive deficits, such as attention problems

- Pallor

- Sensitivity to heat

- Sleep problems

- Other vasomotor symptoms.

Patients who suffer from acute OI usually manifest the disorder by a temporary loss of consciousness and posture, with rapid recovery (simple faints, or syncope), as well as remaining conscious during their loss of posture. This is different from a syncope caused by cardiac problems because there are known triggers for the fainting spell (standing, heat, emotion) and identifiable prodromal symptoms (nausea, blurred vision, headache). As Dr. Julian M. Stewart, an expert in OI from New York Medical College states, "Many syncopal patients have no intercurrent illness; between faints, they are well."

Symptoms:

- Altered vision (blurred vision, "white outs"/gray outs, black outs, double vision)

- Anxiety

- Exercise intolerance

- Fatigue

- Headache

- Heart palpitations, as the heart races to compensate for the falling blood pressure

- Hyperpnea or sensation of difficulty breathing or swallowing (see also hyperventilation syndrome)

- Lightheadedness

- Sweating

- Tremulousness

- Weakness

A classic manifestation of acute OI is a soldier who faints after standing rigidly at attention for an extended period of time.

Existing experimental methods have provided enough evidence to suggest that variations in synaptic serotonin, noradrenaline, and dopamine are significant drivers of central nervous system fatigue. An increased synaptic dopamine concentration in the CNS is strongly ergogenic (promotes exercise performance). An increased synaptic serotonin or noradrenaline concentration in the CNS impairs exercise performance.

A degenerative disease of the autonomic nervous system, symptoms include dizziness and fainting (caused by orthostatic hypotension), visual disturbances and neck pain. Chest pain, fatigue and sexual dysfunction are less common symptoms that may also occur. Symptoms are worse when standing; sometimes one may relieve symptoms by lying down.

The pathology of pure autonomic failure is not yet completely understood. However, a loss of cells in the intermediolateral column of the spinal cord has been documented, as has a loss of catecholamine uptake and catecholamine fluorescence in sympathetic postganglionic neurons. In general, levels of catecholamines in these patients are very low while lying down, and do not increase much upon standing.

The most commonly used diagnostic criteria and definition of CFS for research and clinical purposes were published by the United States Centers for Disease Control and Prevention (CDC). The CDC currently recommends the following criteria for diagnosis:

1. Significantly lowered ability to participate in activities that were routine before the onset of the condition, and persisting more than six months

2. Physical or mental activity causes worsening symptoms that would not have been problematic before the onset of the condition, (post-exertional malaise (PEM))

3. Sleep problems

Additionally, one of the following symptoms must be present:

- Difficulty with thinking and memory

- Worsening of problems with standing or sitting

Other common symptoms may include:

- Muscle pain, joint pain, and headache pain

- Tender lymph nodes in the neck or armpits

- Sore throat

- Irritable bowel syndrome

- Night sweats

- Sensitivities to foods, odors, chemicals, or noise

The CDC proposes that persons with symptoms resembling those of CFS consult a physician to rule out several treatable illnesses: Lyme disease, "sleep disorders, major depressive disorder, alcohol/substance abuse, diabetes, hypothyroidism, mononucleosis (mono), lupus, multiple sclerosis (MS), chronic hepatitis and various malignancies." Medications can also cause side effects that mimic symptoms of CFS. Central sensitization, or increased sensitivity to sensory stimuli such as pain have been observed in CFS. Sensitivity to pain increases post-exertionally, which is opposite to the normal pattern.

The functional capacity of individuals with CFS varies greatly. Some persons with CFS lead relatively normal lives; others are totally bed-ridden and unable to care for themselves. For the majority of persons with CFS, work, school, and family activities are significantly reduced for extended periods of time. The severity of symptoms and disability is the same regardless of gender, and many experience strongly disabling chronic pain. Persons report critical reductions in levels of physical activity. Also, a reduction in the complexity of activity has been observed. Reported impairment is comparable to other fatiguing medical conditions including late-stage AIDS, lupus, rheumatoid arthritis, chronic obstructive pulmonary disease (COPD), and end-stage kidney disease. CFS affects a person's functional status and well-being more than major medical conditions such as multiple sclerosis, congestive heart failure, or type II diabetes mellitus.

Often, there are courses of remission and relapse of symptoms, which make the illness difficult to manage. Persons who feel better for a period may overextend their activities, and the result can be a worsening of their symptoms with a relapse of the illness.

25% of people with CFS are house-bound or bedridden for long periods during their illness, often for decades. An estimated 75% of are unable to work because of their illness. More than half were on disability benefits or temporary sick leave, and less than a fifth worked full-time.

People with CFS have decreased scores on the SF-36 quality of life questionnaire, especially in the sub scales on vitality, physical functioning, general health, physical role and social functioning; however, the sub scales for "role emotional" and mental health in CFS patients were consistent with or not substantially lower than healthy controls. Loss of economic production and costs due to CFS are estimated at between $18 and $51 billion a year in the U.S. Direct healthcare costs are estimated at between $9 and $14 billion annually in the U.S. alone.

The true primary hypersomnias include these: narcolepsy (with and without cataplexy); idiopathic hypersomnia; and recurrent hypersomnias (like Klein-Levin syndrome).

Hypersomnia can be primary (of central/brain origin), or it can be secondary to any of numerous medical conditions. More than one type of hypersomnia can coexist in a single patient. Even in the presence of a known cause of hypersomnia, the contribution of this cause to the complaint of EDS needs to be assessed. When specific treatments of the known condition do not fully suppress EDS, additional causes of hypersomnia should be sought. For example, if a patient with sleep apnea is treated with CPAP (continuous positive airway pressure) which resolves their apneas but not their EDS, it is necessary to seek other causes for the EDS. Obstructive sleep apnea “occurs frequently in narcolepsy and may delay the diagnosis of narcolepsy by several years and interfere with its proper management.”

Functional somatic syndrome is characterized by ambiguous, non-specific symptoms that appear in otherwise-healthy populations. Overlap exists in different syndromes, including gastrointestinal issues, pain, fatigue, cognitive difficulties, and sleep difficulties. Some have proposed to group symptoms into clusters or into one general functional somatic disorder given the finding of correlations between symptoms and underlying etiologies.

Functional somatic syndrome is a term used to refer to physical symptoms that are poorly explained. It encompass disorders such as chronic fatigue syndrome, fibromyalgia, chronic widespread pain, temporomandibular disorder, irritable bowel syndrome, lower back pain, tension headache, atypical face pain, non-cardiac chest pain, insomnia, palpitation, dyspepsia, and dizziness. General overlap exists between this term, somatization, and somatoform.

The defining symptoms of fibromyalgia are chronic widespread pain, fatigue, sleep disturbance, and heightened pain in response to tactile pressure (allodynia). Other symptoms may include tingling of the skin (paresthesias), prolonged muscle spasms, weakness in the limbs, nerve pain, muscle twitching, palpitations, and functional bowel disturbances.

Many people experience cognitive dysfunction (known as "fibrofog"), which may be characterized by impaired concentration, problems with short and long-term memory, short-term memory consolidation, impaired speed of performance, inability to multi-task, cognitive overload, and diminished attention span. Fibromyalgia is often associated with anxiety and depressive symptoms.

Other symptoms often attributed to fibromyalgia that may be due to a comorbid disorder include myofascial pain syndrome, also referred to as chronic myofascial pain, diffuse non-dermatomal paresthesias, functional bowel disturbances and irritable bowel syndrome, genitourinary symptoms and interstitial cystitis, dermatological disorders, headaches, myoclonic twitches, and symptomatic hypoglycemia. Although fibromyalgia is classified based on the presence of chronic widespread pain, pain may also be localized in areas such as the shoulders, neck, low back, hips, or other areas. Many sufferers also experience varying degrees of myofascial pain and have high rates of comorbid temporomandibular joint dysfunction. 20–30% of people with rheumatoid arthritis and systemic lupus erythematosus may also have fibromyalgia.

Fibromyalgia is classed as a disorder of pain processing due to abnormalities in how pain signals are processed in the central nervous system. The American College of Rheumatology classifies fibromyalgia as being a functional somatic syndrome. The expert committee of the European League Against Rheumatism classifies fibromyalgia as a neurobiological disorder and as a result exclusively give pharmacotherapy their highest level of support. The International Classification of Diseases (ICD-10) lists fibromyalgia as a diagnosable disease under "Diseases of the musculoskeletal system and connective tissue," under the code M79-7, and states that fibromyalgia syndrome should be classified as a functional somatic syndrome rather than a mental disorder. Although mental disorders and some physical disorders commonly are co-morbid with fibromyalgia – especially anxiety, depression, irritable bowel syndrome, and chronic fatigue syndrome – the ICD states that these should be diagnosed separately.

Differences in psychological and autonomic nervous system profiles among affected individuals may indicate the existence of fibromyalgia subtypes. A 2007 review divides individuals with fibromyalgia into four groups as well as "mixed types":

1. "extreme sensitivity to pain but no associated psychiatric conditions" (may respond to medications that block the 5-HT3 receptor)

2. "fibromyalgia and comorbid, pain-related depression" (may respond to antidepressants)

3. "depression with concomitant fibromyalgia syndrome" (may respond to antidepressants)

4. "fibromyalgia due to somatization" (may respond to psychotherapy)

Asthenia (Greek: "ἀσθένεια", lit "lack of strength" but also "disease") is a medical term referring to a condition in which the body lacks or has lost strength either as a whole or in any of its parts. It denotes symptoms of physical weakness and loss of strength. General asthenia occurs in many chronic wasting diseases (such as tuberculosis and cancer), sleep disorders or chronic disorders of the heart, lungs or kidneys, and is probably most marked in diseases of the adrenal gland. Asthenia may be limited to certain organs or systems of organs, as in asthenopia, characterized by ready fatiguability. Asthenia is also a side effect of some medications and treatments, such as Ritonavir (a protease inhibitor used in HIV treatment), vaccines such as the HPV vaccine Gardasil and fentanyl patches (an opioid used to treat pain).

Differentiating psychogenic (perceived) asthenia and true asthenia from myasthenia is often difficult, and in time apparent psychogenic asthenia accompanying many chronic disorders is seen to progress into a primary weakness.

Myasthenia (my- from Greek μυο meaning "muscle" + -asthenia ἀσθένεια meaning "weakness"), or simply muscle weakness, is a lack of muscle strength. The causes are many and can be divided into conditions that have either true or perceived muscle weakness. True muscle weakness is a primary symptom of a variety of skeletal muscle diseases, including muscular dystrophy and inflammatory myopathy. It occurs in neuromuscular diseases, such as myasthenia gravis.

Muscle fatigue can be central, neuromuscular, or peripheral muscular. Central muscle fatigue manifests as an overall sense of energy deprivation, and peripheral muscle weakness manifests as a local, muscle-specific inability to do work. Neuromuscular fatigue can be either central or peripheral.

NMT is a diverse disorder. As a result of muscular hyperactivity, patients may present with muscle cramps, stiffness, myotonia-like symptoms (slow relaxation), associated walking difficulties, hyperhidrosis (excessive sweating), myokymia (quivering of a muscle), fasciculations (muscle twitching), fatigue, exercise intolerance, myoclonic jerks and other related symptoms. The symptoms (especially the stiffness and fasciculations) are most prominent in the calves, legs, trunk, and sometimes the face and neck, but can also affect other body parts. NMT symptoms may fluctuate in severity and frequency. Symptoms range from mere inconvenience to debilitating. At least a third of people also experience sensory symptoms.

The symptoms of Dysautonomia, which are numerous and vary widely for each individual, are due to inefficient or unbalanced efferent signals sent via both systems. The primary symptoms in individuals with dysautonomia include

There are three main types of NMT:

- Chronic

- Monophasic (symptoms that resolve within several years of onset; postinfection, postallergic)

- Relapsing Remitting

Caffeine-induced anxiety disorder is an anxiety disorder that can be present in people susceptible to panic attacks and anxiety. Consumption of caffeine has long been linked to anxiety. Caffeine-induced anxiety disorder, however, almost exclusively occurs in people who already have an anxiety disorder. For these people, they are more prone to the psychological effects of caffeine and are at greater risk of a panic attack after ingesting non-trivial amounts of caffeine.

The effects of caffeine and the symptoms of anxiety both increase activity within the sympathetic nervous system. Caffeine has been linked to the aggravation and maintenance of anxiety disorders, and the initiation of panic or anxiety attacks in those who are already predisposed to such phenomena. Caffeine usage surpassing 200 mg has been shown to increase the likelihood for anxiety and panic attacks in a population. Excessive amounts of caffeine can result in symptoms from general anxiety to obsessive-compulsive and phobic symptoms. Anxiety symptoms caused by caffeine are often mistaken for serious mental disorders including bipolar disorder and schizophrenia, leaving patients medicated for the wrong issue.

Dysautonomia may be due to inherited or degenerative neurologic diseases (primary dysautonomia) or it may occur due to injury of the autonomic nervous system from an acquired disorder (secondary dysautonomia). The most common causes of dysautonomia include

In the sympathetic nervous system (SNS), predominant dysautonomia is common along with fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome, and interstitial cystitis, raising the possibility that such dysautonomia could be their common clustering underlying pathogenesis.

In addition to sometimes being a symptom of dysautonomia, anxiety can sometimes physically manifest symptoms resembling autonomic dysfunction. A thorough investigation ruling out physiological causes is crucial, but in cases where relevant tests are performed and no causes are found or symptoms do not match any known disorders, a primary anxiety disorder is possible, but should not be presumed. For such patients, the anxiety sensitivity index may have better predictivity for anxiety disorders, while the Beck anxiety inventory may misleadingly suggest anxiety for patients with dysautonomia.

Central nervous system depression or CNS depression refers to physiological depression of the central nervous system that can result in decreased rate of breathing, decreased heart rate, and loss of consciousness possibly leading to coma or death. CNS depression is specifically the result of inhibited brain activity.

Four cardinal symptoms have sometimes been used as diagnostic criteria:

1. painful, fatty lipomas (benign fatty tumors) across anatomy

2. obesity, frequently in menopausal age

3. weakness and fatigue

4. emotional instability, depression, epilepsy, confusion, and dementia.

There are also potential signs of the disease which are identified as the following:

However, as it is unclear which symptoms are cardinal and which symptoms are minor signs in Dercum's disease, it is unclear which should be used as diagnostic criteria. Researchers have proposed a 'minimal definition' based on symptoms most often part of Dercum's disease: 1) Generalized overweight or obesity. 2) Chronic pain in the adipose tissue. The associated symptoms in Dercum's disease include obesity, fatty deposits, easy bruisability, sleep disturbances, impaired memory, depression, difficulty concentrating, anxiety, rapid heartbeat, shortness of breath, diabetes, bloating, constipation, fatigue, weakness and joint and muscle aches. Regarding the associated symptoms in Dercum's disease, only case reports have been published. No study involving medical examinations has been performed in a large group of patients.

Acute TM is rarer than chronic TM and symptoms appear within days of onset. Acute TM degrades muscle fibers rapidly. Due to the rapid degradation of muscle fibers patients usually cite severe muscle cramps and muscle pain. Some acute TM patients may present symptoms of blurred vision and bulging eyes due to eye muscle degradation and inflammation, but documented cases are rare. Acute TM patients usually have very weak respiratory muscles and often severe respiratory failure occurs.

Symptoms of chronic TM arise slowly. Patients usually cite decreased exercise tolerance, increased fatigue, and difficulty completing certain tasks after six months of onset. If chronic TM goes untreated worse symptoms may develop including difficulty swallowing and respiratory distress. These occurrences are rare since diagnosis of chronic TM usually occurs during the early stages of onset, before these symptoms develop.