[7] Untreated, and over years to decades, CTS causes loss of sensibility, weakness, and shrinkage (atrophy) of the thenar muscles at the base of the thumb.

[14] This line uses surface landmarks, and is drawn between the apex of the skin fold between the thumb and index finger to the palpated hamate hook.

[16] Theoretically, increased pressure can interfere with normal intraneural blood flow, eventually causing a cascade of physiological changes in the nerve itself.

[17] The symptoms and signs of carpal tunnel syndrome causes are hypertrophy of the synovial tissue surrounding the flexor tendons such as with rheumatoid arthritis.

Severe carpal tunnel syndrome patients may have degree II/III injuries (Sunderland classification), or axonotmesis, where the axon is injured partially or fully.

The characteristic symptom of CTS is numbness, tingling, or burning sensations in the thumb, index, middle, and radial half of the ring finger.

[38] A person with idiopathic carpal tunnel syndrome will not have any sensory loss over the thenar eminence (bulge of muscles in the palm of hand and at the base of the thumb).

CTS can be detected on examination using one of several maneuvers to provoke paresthesia (a sensation of tingling or "pins and needles" in the median nerve distribution).

These so-called provocative signs include: Diagnostic performance characteristics such as sensitivity and specificity are reported, but difficult to interpret because of the lack of a consensus reference standard for CTS.

[43] Some other factors that contribute to carpal tunnel syndrome are conditions such as diabetes, alcoholism, vitamin deficiency or toxicity as well as exposure to toxins.

[49] There is consideration that bilateral carpal tunnel syndrome could be a reason to consider amyloidosis, timely diagnosis of which could improve heart health.

The Occupational Safety and Health Administration (OSHA) has adopted rules and regulations regarding so-called "cumulative trauma disorders" based concerns regarding potential harm from exposure to repetitive tasks, force, posture, and vibration.

[57][58] A review of available scientific data by the National Institute for Occupational Safety and Health (NIOSH) indicated that job tasks that involve highly repetitive manual acts or specific wrist postures were associated with symptoms of CTS, but there was not a clear distinction of paresthesia (appropriate) from pain (inappropriate) and causation was not established.

[65] There is speculation that repetitive flexion and extension in the wrist can cause thickening of the synovial tissue that lines the tendons within the carpal tunnel.

[66] A variety of patient factors can lead to CTS, including heredity, size of the carpal tunnel, associated local and systematic diseases, and certain habits.

A combination of characteristic symptoms (how it feels) and signs (what the clinician finds on exam) are associated with a high probability of CTS without electrophysiological testing.

Notable CTS should remind clinicians to always consider the whole person, including their mindset and circumstances, in strategies to help people get and stay healthy.

The AANEM has issued evidence-based practice guidelines for the diagnosis of carpal tunnel syndrome, both by electrodiagnostic studies and by neuromuscular ultrasound.

[5] Carpal tunnel syndrome is sometimes applied as a label to anyone with pain, numbness, swelling, or burning in the radial side of the hands or wrists.

[10] When the symptoms and signs point to atrophy and muscle weakness more than numbness, consider neurodegenerative disorders such as Amyotrophic Lateral Sclerosis or Charcot-Marie Tooth.

[80] Some claim that worksite modifications such as switching from a QWERTY computer keyboard layout to Dvorak is helpful, but meta-analyses of the available studies note limited supported evidence.

Early surgery with carpal tunnel release is indicated where there is evidence of median nerve denervation or a person elects to proceed directly to surgical treatment.

[107] A randomized control trial published in 2017 sought to examine the efficacy of manual therapy techniques for the treatment of carpal tunnel syndrome.

In cases of epineural tethering in the upper extremity, manual therapy can reduce this dysfunction and can have a positive impact on the gliding of the nerves through the carpal tunnel while moving the elbow, fingers, or wrist.

[109] Self-myofascial ligament stretching has been suggested as an effective technique, although a meta-analysis claimed this kind of therapy does not show significant improvement in symptoms or function.

Atrophy of the thenar muscles, weakness of palmar abduction, and loss of sensibility (constant numbness as opposed to intermittent paresthesia) are signs of advanced neuropathy.

[113] Paresthesia may increase after release of advanced carpal tunnel syndrome, and people may feel worse than they did prior to surgery for many months.

[115][116] Caution is warranted in considering additional surgery for people dissatisfied with the result of carpal tunnel release as perceived recurrence may more often be due to renewed awareness of persistent symptoms rather than worsening pathology.

The first to notice the association between the carpal ligament pathology and median nerve compression appear to have been Pierre Marie and Charles Foix in 1913.

[125] Physician George S. Phalen of the Cleveland Clinic drew attention to the pathology of compression as the reason for CTS after working with a group of patients in the 1950s and 1960s.