Carpal tunnel syndrome (CTS) is the symptoms and signs characteristic of compressive median neuropathy at the carpal tunnel of the wrist. Compressive median neuropathy is a structural, largely hereditary condition that is usually measurable in both wrists. Most cases of median neuropathy at the carpal tunnel are idiopathic, meaning there is no known cause. Other causes of median nerve compression at the carpal tunnel include bleeding, swelling, and deformity associated with a wrist fracture. Carpal tunnel syndrome can also occur with rheumatoid arthritis, due to the enlarged synovial lining of the tendons causing median nerve compression.
The main symptoms are numbness and tingling of the thumb, index finger, middle finger, and the thumb side of the ring finger, as well as pain in the hand and fingers. Symptoms are typically most troublesome at night. Many people sleep with their wrists bent, and the ensuing symptoms may lead to awakening. People wake less often at night if they wear a wrist splint. Untreated, and over years to decades, CTS causes loss of sensitivity, weakness, and shrinkage (atrophy) of the thenar muscles at the base of the thumb.
Work-related factors such as vibration, wrist extension or flexion, hand force, and repetitive strain are risk factors for CTS. Other risk factors include being female, obesity, diabetes, rheumatoid arthritis, thyroid disease, and genetics.
Diagnosis can be made with a high probability based on characteristic symptoms and signs. It can also be measured with electrodiagnostic tests.
Injection of corticosteroids may or may not alleviate symptoms better than simulated (placebo) injections. There is no evidence that corticosteroid injection sustainably alters the natural history of the disease, which seems to be a gradual progression of neuropathy. Surgery to cut the transverse carpal ligament is the only known disease modifying treatment.
Anatomy
The carpal tunnel is an anatomical compartment located at the base of the palm. Nine flexor tendons and the median nerve pass through the carpal tunnel, which is surrounded on three sides by the carpal bones that form an arch. The median nerve provides feeling or sensation to the thumb, index finger, long finger, and half of the ring finger. At the level of the wrist, the median nerve supplies the muscles at the base of the thumb that allow it to abduct, move away from the other four fingers, as well as move out of the plane of the palm. The carpal tunnel is located at the middle third of the base of the palm, bounded by the bony prominence of the scaphoid tubercle and trapezium at the base of the thumb, and the hamate hook that can be palpated along the axis of the ring finger. From the anatomical position, the carpal tunnel is bordered on the anterior surface by the transverse carpal ligament, also known as the flexor retinaculum. The flexor retinaculum is a strong, fibrous band that attaches to the pisiform and the hamulus of the hamate. The proximal boundary is the distal wrist skin crease, and the distal boundary is approximated by a line known as Kaplan's cardinal line. 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.
Pathophysiology
The carpal bones and the transverse carpal ligament form the carpal tunnel. The median nerve passes through this space along with the flexor tendons. Increased compartmental pressure for any reason can squeeze the median nerve. Theoretically, increased pressure can interfere with normal intraneural blood flow, eventually causing a cascade of physiological changes in the nerve itself. There is a dose-respondent curve such that greater and longer periods of pressure are associated with greater nerve dysfunction. The symptoms and signs of carpal tunnel syndrome causes are hypertrophy of the synovial tissue surrounding the flexor tendons such as with rheumatoid arthritis.
Prolonged pressure can lead to a cascade of physiological changes in neural tissue. First, the blood-nerve barrier breaks down (increased permeability of perineureum and endothelial cells of endoneural blood vessels). If the pressure continues, the nerves will start the process of demyelination under the area of compression. This will result in abnormal nerve conduction even when the pressure is relieved leading to persistent sensory symptoms until remyelination can occur. If the compression continues and is severe enough, axons may be injured and Wallerian degeneration will occur. At this point there may be weakness and muscle atrophy, depending on the extent of axon damage.
The critical pressure above which the microcirculatory environment of a nerve becomes compromised depends on diastolic/systolic blood pressure. Higher blood pressure will require higher external pressure on the nerve to disrupt its microvascular environment. The critical pressure necessary to disrupt the blood supply of a nerve is approximately 30mm Hg below diastolic blood pressure or 45mm Hg below mean arterial pressure. For normohypertensive (normal blood pressure) adults, the average values for systolic blood pressure is 116mm Hg diastolic blood pressure is 69mm Hg. Using this data, the average person would become symptomatic with approximately 39mm Hg of pressure in the wrist (69 - 30 = 39 and 69 + (116 - 69)/3 - 45 ~ 40). Carpal tunnel syndrome patients tend to have elevated carpal tunnel pressures (12-31mm Hg) compared to controls (2.5 - 13mm Hg). Applying pressure to the carpal tunnel of normal subjects in a lab can produce mild neurophysiological changes at 30mm Hg with a rapid, complete sensory block at 60mm Hg. Carpal tunnel pressure may be affected by wrist movement/position, with flexion and extension capable of raising the tunnel pressure as high as 111mm Hg. Many of the activities associated with carpal tunnel symptoms such as driving, holding a phone, etc. involve flexing the wrist and it is likely due to an increase in carpal tunnel pressure during these activities.
Nerve compression can result in various stages of nerve injury. The majority of carpal tunnel syndrome patients have a degree I nerve injury (Sunderland classification), also called neuropraxia. This is characterized by a conduction block, segmental demyelination, and intact axons. With no further compression, the nerves will remyelinate and fully recover. Severe carpal tunnel syndrome patients may have degree II/III injuries (Sunderland classification), or axonotmesis, where the axon is injured partially or fully. With axon injury, there would be muscle weakness or atrophy, and with no further compression, the nerves may only partially recover.
While there is evidence that chronic compression is a major cause of carpal tunnel syndrome, it may not be the only cause. Nerve scarring (specifically adherence between the mesoneurium and epineureum) may prevent the nerve from gliding during wrist or finger movements, causing repetitive traction injuries. Another is the double crush syndrome, where compression may interfere with axonal transport, and two separate points of compression (e.g. neck and wrist), neither enough to cause local demyelination, may together impair normal nerve function.
Epidemiology Carpal tunnel syndrome is estimated to affect one out of ten people during their lifetime and is the most common nerve compression syndrome. There is notable variation in such estimates based on how one defines the problem, in particular, whether one studies people presenting with symptoms vs. measurable median neuropathy, whether or not people are seeking care. Idiopathic neuropathy accounts for about 90% of all nerve compression syndromes.
Signs and symptoms The characteristic symptom is numbness, tingling, or burning sensations in the thumb, index, middle, and radial half of the ring finger. These areas process sensation through the median nerve. Numbness or tingling is usually worse with sleep. People tend to sleep with their wrists flexed, which increases pressure on the nerve. Ache and discomfort may be reported in the forearm or even the upper arm. Page last reviewed: 18/09/2014 Symptoms that are not as characteristic of CTS include pain in the wrists or hands, loss of grip strength, minor loss of sleep, and loss of manual dexterity.
Severe CTS is associated with measurable loss of sensibility. As the median neuropathy progresses, there is loss of sensibility in the thumb, index, middle, and the thumb side of the ring finger. As the neuropathy progresses, there may be first weakness, then atrophy of the muscles of thenar eminence (the flexor pollicis brevis, opponens pollicis, and abductor pollicis brevis). The sensibility of the palm remains normal because the superficial sensory branch of the median nerve branches proximal to the transverse carpal ligament (TCL) and travels superficial to it.
Median nerve symptoms may arise from nerve compression at the level of the thoracic outlet or the area where the median nerve passes between the two heads of the pronator teres in the forearm, although this is debated.
Severe CTS is also associated with weakness and atrophy of the muscles at the base of the thumb. The ability to abduct the thumb may be lost.
A person with idiopathic carpal tunnel syndrome will not have any sensory loss over the thenar eminence (bulge of muscles in the palm of the hand and at the base of the thumb). This is because the palmar branch of the median nerve, which innervates that area of the palm, separates from the median nerve and passes over the carpal tunnel.
Causes
Most presentations of CTS have no known disease cause (idiopathic).
The association of other factors with CTS is a source of notable debate. It is important to distinguish factors that provoke symptoms and factors that are associated with seeking care from factors that make the neuropathy worse.
Genetic factors are believed to be the most important determinants of who develops carpal tunnel syndrome. In other words, one's wrist structure seems programmed at birth to develop CTS later in life. A genome-wide association study (GWAS) of carpal tunnel syndrome identified 50 genomic loci significantly associated with the disease, including several loci previously known to be associated with human height.
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. Conditions such as these don't necessarily increase the interstitial pressure of the carpal tunnel. One case-control study noted that individuals classified as obese (BMI >29) are 2.5 times more likely than slender individuals (BMI <20) to be diagnosed with CTS. It is not clear whether this association is due to an alteration of pathophysiology, a variation in symptoms, or a variation in care-seeking.
Discrete pathophysiology and CTS
Hereditary neuropathy with susceptibility to pressure palsies is a genetic condition that appears to increase the probability of developing CTS. Heterozygous mutations in the gene SH3TC2, associated with Charcot-Marie-Tooth, may confer susceptibility to neuropathy, including CTS.