Carpal tunnel syndrome (CTS) is the most common focal peripheral neuropathy. CTS is caused by entrapment of the median nerve at the wrist as it traverses through the carpal tunnel.
Acute CTS is a rare compartment syndrome of the carpal tunnel that occurs after major trauma, typically distal radius fracture. Diagnosis is based on clinical history and examination and does not require electrophysiological testing to proceed with surgery as soon as possible to relieve the pressure on the median nerve. [1, 2, 3]
Chronic CTS is a much more common condition and of more gradual onset, with intermittent symptoms initially and slow progression. The condition is often bilateral and almost always more prominent in the dominant hand. The syndrome is characterized by pain, paresthesia, and weakness in the median nerve distribution of the hand that are typically provoked by sleep or activities involving repetitive hand use. Electrodiagnostic studies are helpful to confirm the diagnosis. Treatment in mild cases may be nonsurgical and includes wrist splinting, but many patients require either open or endoscopic carpal tunnel release surgery with usually excellent outcome.
The median nerve is formed by C5-C7 fibers from the lateral cord and C8-T1 fibers from the medial cord of the brachial plexus. Muscular branches of the median nerve innervate most of the forearm flexor muscles and include the anterior interosseus nerve. The palmar cutaneous branch of the median nerve leaves the main trunk proximal to the wrist crease and provides sensation over the thenar eminence. See the image below.
Within the hand, the median nerve carries C8-T1 motor fibers to the abductor pollicis brevis, opponens pollicis, and superficial head of the flexor pollicis brevis muscles (thenar or recurrent motor branch) and the first and second lumbrical muscles. It supplies sensory innervation to the palmar surface of the thumb, and digits 2, 3, and the lateral half of digit 4 (via the common palmar digits nerves 1-3).
The median nerve crosses from the distal forearm to the hand through the carpal tunnel. The carpal tunnel is located at the base of the palm, just distal to the distal wrist crease. The floor of the carpal tunnel is formed by the carpal bones that create an arch. The fibrous flexor retinaculum, or transverse carpal ligament (TCL), is the roof of the carpal tunnel on the palmar side. The carpal tunnel is the narrowest at the level of the distal carpal row, at the level of the hook of the hamate bone. Within the carpal tunnel, the median nerve is physiologically flattened in configuration, and this flattening is maximal about 2-2.5 cm distal to the proximal edge of TCL. Along with the median nerve, 9 flexor digitorum tendons (8 tendons of the superficial and deep finger flexors and 1 of the flexor pollicis longus) pass through the carpal tunnel. The TCL is under tension, helps to maintain the carpal arch, and provides a retinacular pulley to the flexor tendons. See the image below.
CTS is caused by increased pressure in the carpal tunnel and on the median nerve. Compression of a peripheral nerve induces marked changes in intraneural microcirculation and nerve fiber structure, impairment of axonal transport, and alterations in vascular permeability, with edema formation and deterioration of nerve function.  Ischemia is a more significant factor of nerve fiber damage in acute median nerve compression, whereas in chronic entrapment, mechanical distortion plays a greater role. The pathology of idiopathic CTS is a noninflammatory fibrosis of the subsynovial connective tissue surrounding the flexor tendons. Biochemical studies of surgical specimens suggest that a variety of regulatory molecules may be inducing fibrous and vascular proliferation and that this may be a response to mechanical stresses. 
In a study of patients with CTS, when the wrist was in neutral position, the mean pressure in the carpal canal was 32 mm Hg versus 2.5 mm Hg in healthy patients.  The pressure increased to 94 mm Hg during wrist flexion (healthy patients 32 mm Hg) and 110 mm Hg during wrist extension (healthy patients 30 mm Hg). Carpal tunnel release brought about an immediate and sustained reduction in pressure.
In animal experiments, acute and severe compression caused persistent impairment of intraneural microcirculation due to mechanical injury to blood vessels.  In rabbits undergoing a graded compression of the tibial nerve, interference with venular flow was observed at a pressure of 20-30 mm Hg, while arteriolar and intrafascicular capillary flow was impaired at about 40-50 mm Hg. At 60-80 mm Hg, no blood flow ceased completely. 
In early or mild CTS, the median nerve has no morphological changes, and neurologic symptoms are intermittent. Prolonged increased pressure on the nerve results in segmental demyelination. The focal demyelination causes short segment conduction delay or conduction block across the site of entrapment. In more severe cases, wallerian degeneration and denervation of the thenar muscles develops.
The peripheral nerves of patients with underlying generalized neuropathies are more susceptible to compression injury, and the condition is associated in up to one third of cases with systemic medical conditions. Most cases of CTS are considered idiopathic. Some patients have an inherited increased susceptibility of the nerve to pressure, and on rare occasions CTS may be familial.
The concept of double crush syndrome was introduced in 1973 by Upton and McComas.  They proposed that focal compression of the nerve proximally predisposes it to injury at a more distal site along its course through impaired axoplasmic flow. The hypothesis remains of uncertain validity; there is no clear association between the frequency and severity of CTS and level of cervical radiculopathy. 
CTS is the most common focal peripheral neuropathy. The reported incidence varies by location and methodology used. Prevalence rates for CTS are reported as 1-5% in the general population and 5-15% in the industrial settings. An increasing temporal trend has been reported in several studies. [10, 11]
According to data from the 1980s, the prevalence of electrophysiologically confirmed symptomatic CTS is about 3% among women and 2% among men. 
A cross-sectional survey reported in 2001 calculated the lowest possible prevalence of symptomatic CTS in the general US population as 3.72%. 
Among residents of Olmsted County, Minnesota, the adjusted annual rates of medically diagnosed CTS increased from 258/100,000 in 1981-1985 to 424/100,000 in 2000-2005.  For this last period included in the study, the incidence in women was 542/100,000 and in men was 303/100,000. Generally, the most marked increases in CTS incidence were seen in younger age groups of both sexes in the first part of the study period and among older age groups in the final decades of study. The cause of the increase is unclear, but it corresponds to an epidemic of CTS cases resulting in lost work days that began in the mid 1980s and lasted through the mid 1990s. The elderly present with more severe disease and are more likely to have carpal tunnel surgery. 
In the general population for a Dutch community, the prevalence rate of undetected CTS was 5.8% in adult women, and an additional 3.4% already carried the diagnosis of CTS. The overall prevalence rate for men was 0.6%. 
A primary care study in the UK from 2000 reported an annual incidence of CTS of 88/100,000 in men, and 193/100,000 in women. New presentations were most frequent in women aged 45-54 years.  In this study, CTS was as common as all other entrapment neuropathies combined.
A study in Italy reported a mean standardized annual incidence of 329/100,000 in the Siena area (Tuscany) from 1991-1998, with 139 for men and 506 for women. The age-specific incidence for women increased gradually with age, reaching a peak from 50-59 years. In men, there was a bimodal distribution with peaks from 50-59 years and 70-79 years. 
A French study of CTS from 2002-2004 in patients aged 20-59 years reported a mean incidence rate per 1000 person-years that was higher in employed than unemployed persons (1.7 vs 0.8 in women and 0.6 vs 0.3 in men). Higher values were blue-collar workers and lower-grade services, sales, and clerical white-collar workers. 
CTS is associated with high costs to the Health Care system and society. According to 1988 data from the United States, every year an estimated 1 million adults require medical treatment for CTS.  About 400,000-500,000 CTS surgeries annually were reported in 1995 with an economic cost of more than 2 billion. 
In 1999, CTS cases were associated with a median number of 27 days lost from work, the highest number of any major disabling illness or injury. 
Findings of the 1988 National Health Interview survey indicate that CTS is 1.8 times more prevalent in whites than nonwhites.
The reported female-to-male ratio ranges from 3:1 to about 10:1. Phalen’s original series in 1970 included 280 women and 96 men (female-to-male ratio 3:1). 
Of the patients in Phalen’s series, 58% were adults aged 40-60 years. 
A general population survey in Rochester, Minn., showed the age-adjusted incidence of carpal tunnel syndrome to be 105 cases per 100,000 person-years. Age-adjusted incidence rates were 52 cases per 100,000 person-years for men and 149 cases per 100,000 person-years for women. The study showed that the incidence increased from 88 cases per 100,000 person-years between 1961 and 1965 to 125 cases per 100,000 person-years between 1976 and 1980. The incidence increased with age in men, whereas it peaked at 45 to 54 years of age in women. Carpal tunnel syndrome is possibly the most common nerve disorder experienced today. It affects 4 – 10 million Americans. Middle-aged to older individuals are more likely to develop the syndrome than younger persons, and females three times more frequently than males. [21, 22]
Yoshii Y, Tung WL, Ishii T. Strain and Morphological Changes of Median Nerve After Carpal Tunnel Release. J Ultrasound Med. 2017 Jun. 36 (6):1153-1159. [Medline].
Ordahan B, Karahan AY. Efficacy of paraffin wax bath for carpal tunnel syndrome: a randomized comparative study. Int J Biometeorol. 2017 Dec. 61 (12):2175-2181. [Medline].
Marquardt TL, Evans PJ, Seitz WH Jr, Li ZM. Carpal arch and median nerve changes during radioulnar wrist compression in carpal tunnel syndrome patients. J Orthop Res. 2016 Jul. 34 (7):1234-40. [Medline]. [Full Text].
Lundborg G, Dahlin LB. The pathophysiology of nerve compression. Hand Clin. 1992 May. 8(2):215-27. [Medline].
Bland JD. Carpal tunnel syndrome. Curr Opin Neurol. 2005 Oct. 18(5):581-5. [Medline].
Gelberman RH, Hergenroeder PT, Hargens AR, Lundborg GN, Akeson WH. The carpal tunnel syndrome. A study of carpal canal pressures. J Bone Joint Surg Am. 1981 Mar. 63(3):380-3. [Medline].
Rydevik B, Lundborg G, Bagge U. Effects of graded compression on intraneural blood blow. An in vivo study on rabbit tibial nerve. J Hand Surg Am. 1981 Jan. 6(1):3-12. [Medline].
Upton AR, McComas AJ. The double crush in nerve entrapment syndromes. Lancet. 1973 Aug 18. 2(7825):359-62. [Medline].
Kwon HK, Hwang M, Yoon DW. Frequency and severity of carpal tunnel syndrome according to level of cervical radiculopathy: double crush syndrome?. Clin Neurophysiol. 2006 Jun. 117(6):1256-9. [Medline].
Mondelli M, Giannini F, Giacchi M. Carpal tunnel syndrome incidence in a general population. Neurology. 2002 Jan 22. 58(2):289-94. [Medline].
Gelberman RH, Rydevik BL, Pess GM, Szabo RM, Lundborg G. Carpal tunnel syndrome. A scientific basis for clinical care. Orthop Clin North Am. 1988 Jan. 19(1):115-24. [Medline].
Papanicolaou GD, McCabe SJ, Firrell J. The prevalence and characteristics of nerve compression symptoms in the general population. J Hand Surg Am. 2001 May. 26(3):460-6. [Medline].
de Krom MC, Knipschild PG, Kester AD, Thijs CT, Boekkooi PF, Spaans F. Carpal tunnel syndrome: prevalence in the general population. J Clin Epidemiol. 1992 Apr. 45(4):373-6. [Medline].
Roquelaure Y, Ha C, Pelier-Cady MC, Nicolas G, Descatha A, Leclerc A, et al. Work increases the incidence of carpal tunnel syndrome in the general population. Muscle Nerve. 2008 Apr. 37(4):477-82. [Medline].
Tanaka S, Wild DK, Seligman PJ, Behrens V, Cameron L, Putz-Anderson V. The US prevalence of self-reported carpal tunnel syndrome: 1988 National Health Interview Survey data. Am J Public Health. 1994 Nov. 84(11):1846-8. [Medline]. [Full Text].
Palmer DH, Hanrahan LP. Social and economic costs of carpal tunnel surgery. Instr Course Lect. 1995. 44:167-72. [Medline].
Phalen GS. Reflections on 21 years’ experience with the carpal-tunnel syndrome. JAMA. 1970 May 25. 212(8):1365-7. [Medline].
Nigel Ashworth. Carpal Tunnel Syndrome. www.aafp.org. Available at https://www.aafp.org/afp/2007/0201/p381.html. 2007 Feb 01;
Luke Barre. Carpal Tunnel Syndrome. www.rheumatology.org. Available at https://www.rheumatology.org/I-Am-A/Patient-Caregiver/Diseases-Conditions/Carpal-Tunnel-Syndrome. Accessed: March 2017.
Katz JN, Larson MG, Sabra A, Krarup C, Stirrat CR, Sethi R. The carpal tunnel syndrome: diagnostic utility of the history and physical examination findings. Ann Intern Med. 1990 Mar 1. 112(5):321-7. [Medline].
D’Arcy CA, McGee S. The rational clinical examination. Does this patient have carpal tunnel syndrome?. JAMA. 2000 Jun 21. 283(23):3110-7. [Medline].
MacDermid JC, Wessel J. Clinical diagnosis of carpal tunnel syndrome: a systematic review. J Hand Ther. 2004 Apr-Jun. 17(2):309-19. [Medline].
Burke DT, Burke MA, Bell R, Stewart GW, Mehdi RS, Kim HJ. Subjective swelling: a new sign for carpal tunnel syndrome. Am J Phys Med Rehabil. 1999 Nov-Dec. 78(6):504-8. [Medline].
Johnson EW, Gatens T, Poindexter D, Bowers D. Wrist dimensions: correlation with median sensory latencies. Arch Phys Med Rehabil. 1983 Nov. 64(11):556-7. [Medline].
Kuhlman KA, Hennessey WJ. Sensitivity and specificity of carpal tunnel syndrome signs. Am J Phys Med Rehabil. 1997 Nov-Dec. 76(6):451-7. [Medline].
Radecki P. A gender specific wrist ratio and the likelihood of a median nerve abnormality at the carpal tunnel. Am J Phys Med Rehabil. 1994 Jun. 73(3):157-62. [Medline].
de Krom MC, Knipschild PG, Kester AD, Spaans F. Efficacy of provocative tests for diagnosis of carpal tunnel syndrome. Lancet. 1990 Feb 17. 335(8686):393-5. [Medline].
Durkan JA. A new diagnostic test for carpal tunnel syndrome. J Bone Joint Surg Am. 1991 Apr. 73(4):535-8. [Medline].
LaBan MM, Friedman NA, Zemenick GA. “Tethered” median nerve stress test in chronic carpal tunnel syndrome. Arch Phys Med Rehabil. 1986 Nov. 67(11):803-4. [Medline].
Raudino F. Tethered median nerve stress test in the diagnosis of carpal tunnel syndrome. Electromyogr Clin Neurophysiol. 2000 Jan-Feb. 40(1):57-60. [Medline].
Fleckenstein JL, Wolfe GI. MRI vs EMG: which has the upper hand in carpal tunnel syndrome?. Neurology. 2002 Jun 11. 58(11):1583-4. [Medline].
Stein D, Neufeld A, Pasternak O, Graif M, Patish H, Schwimmer E, et al. Diffusion tensor imaging of the median nerve in healthy and carpal tunnel syndrome subjects. J Magn Reson Imaging. 2009 Mar. 29(3):657-62. [Medline].
Khalil C, Hancart C, Le Thuc V, Chantelot C, Chechin D, Cotten A. Diffusion tensor imaging and tractography of the median nerve in carpal tunnel syndrome: preliminary results. Eur Radiol. 2008 Oct. 18(10):2283-91. [Medline].
Andreisek G, White LM, Kassner A, Sussman MS. Evaluation of diffusion tensor imaging and fiber tractography of the median nerve: preliminary results on intrasubject variability and precision of measurements. AJR Am J Roentgenol. 2010 Jan. 194(1):W65-72. [Medline].
[Guideline] Jablecki CK, Andary MT, Floeter MK, Miller RG, Quartly CA, Vennix MJ, et al. Practice parameter: Electrodiagnostic studies in carpal tunnel syndrome. Report of the American Association of Electrodiagnostic Medicine, American Academy of Neurology, and the American Academy of Physical Medicine and Rehabilitation. Neurology. 2002 Jun 11. 58(11):1589-92. [Medline]. [Full Text].
Robinson LR, Micklesen PJ, Wang L. Strategies for analyzing nerve conduction data: superiority of a summary index over single tests. Muscle Nerve. 1998 Sep. 21(9):1166-71. [Medline].
Chang MH, Liu LH, Lee YC, Wei SJ, Chiang HL, Hsieh PF. Comparison of sensitivity of transcarpal median motor conduction velocity and conventional conduction techniques in electrodiagnosis of carpal tunnel syndrome. Clin Neurophysiol. 2006 May. 117(5):984-91. [Medline].
Robinson LR, Micklesen PJ, Wang L. Optimizing the number of tests for carpal tunnel syndrome. Muscle Nerve. 2000 Dec. 23(12):1880-2. [Medline].
Lew HL, Wang L, Robinson LR. Test-retest reliability of combined sensory index: implications for diagnosing carpal tunnel syndrome. Muscle Nerve. 2000 Aug. 23(8):1261-4. [Medline].
[Guideline] American Academy of Orthopaedic Surgeons. American Academy of Orthopaedic Surgeons clinical practice guideline on the treatment of carpal tunnel syndrome. National Guideline Clearinghouse. Available at http://guideline.gov/content.aspx?id=13304. Accessed: December 23, 2009.
Gooch CL, Mitten DJ. Treatment of carpal tunnel syndrome: is there a role for local corticosteroidinjection?. Neurology. 2005 Jun 28. 64(12):2006-7. [Medline].
Moghtaderi AR, Jazayeri SM, Azizi S. EMLA cream for carpal tunnel syndrome: how it compares with steroid injection. Electromyogr Clin Neurophysiol. 2009 Sep-Oct. 49(6-7):287-9. [Medline].
Katz JN, Simmons BP. Clinical practice. Carpal tunnel syndrome. N Engl J Med. 2002 Jun 6. 346(23):1807-12. [Medline].
Senger JL, Classen D, Bruce G, Kanthan R. Fibrolipomatous hamartoma of the median nerve: A cause of acute bilateral carpal tunnel syndrome in a three-year-old child: A case report and comprehensive literature review. Can J Plast Surg. 2014 Fall. 22(3):201-6. [Medline]. [Full Text].
Verdugo RJ, Salinas RA, Castillo JL, Cea JG. Surgical versus non-surgical treatment for carpal tunnel syndrome. Cochrane Database Syst Rev. 2008 Oct 8. CD001552. [Medline].
Hui AC, Wong S, Leung CH, et al. A randomized controlled trial of surgery vs steroid injection for carpal tunnelsyndrome. Neurology. 2005 Jun 28. 64(12):2074-8. [Medline].
Jarvik JG, Comstock BA, Kliot M, Turner JA, Chan L, Heagerty PJ, et al. Surgery versus non-surgical therapy for carpal tunnel syndrome: a randomised parallel-group trial. Lancet. 2009 Sep 26. 374(9695):1074-81. [Medline].
Tosti R, Ilyas AM. Acute carpal tunnel syndrome. Orthop Clin North Am. 2012 Oct. 43(4):459-65. [Medline].
Hankins CL. Carpal tunnel syndrome caused by a fibrolipomatous hamartoma of the median nerve treated by endoscopic release of the carpal tunnel. J Plast Surg Hand Surg. 2012 Apr. 46(2):124-7. [Medline].
Scholten RJ, Mink van der Molen A, Uitdehaag BM, Bouter LM, de Vet HC. Surgical treatment options for carpal tunnel syndrome. Cochrane Database Syst Rev. 2007 Oct 17. CD003905. [Medline].
Jimenez DF, Gibbs SR, Clapper AT. Endoscopic treatment of carpal tunnel syndrome: a critical review. J Neurosurg. 1998 May. 88(5):817-26. [Medline].
Di Geronimo G, Caccese AF, Caruso L, Soldati A, Passaretti U. Treatment of carpal tunnel syndrome with alpha-lipoic acid. Eur Rev Med Pharmacol Sci. 2009 Mar-Apr. 13(2):133-9. [Medline].
Chang MH, Chiang HT, Lee SS, et al. Oral drug of choice in carpal tunnel syndrome. Neurology. 1998 Aug. 51(2):390-3. [Medline].
Chang MH, Ger LP, Hsieh PF, Huang SY. A randomised clinical trial of oral steroids in the treatment of carpal tunnel syndrome: a long term follow up. J Neurol Neurosurg Psychiatry. 2002 Dec. 73(6):710-4. [Medline]. [Full Text].
Yang CP, Hsieh CL, Wang NH, Li TC, Hwang KL, Yu SC, et al. Acupuncture in patients with carpal tunnel syndrome: A randomized controlled trial. Clin J Pain. 2009 May. 25(4):327-33. [Medline].
Altrocchi PH, Daube JR, Frishberg BM. Practice parameter: carpal tunnel syndrome. Neurology. 1993. 43(11):2406-9.
Campagna R, Pessis E, Feydy A, Guerini H, Le Viet D, Corlobé P, et al. MRI assessment of recurrent carpal tunnel syndrome after open surgical release of the median nerve. AJR Am J Roentgenol. 2009 Sep. 193(3):644-50. [Medline].
Campbell WW. Diagnosis and management of common compression and entrapment neuropathies. Neurol Clin. 1997 Aug. 15(3):549-67. [Medline].
Durkan JA. A new diagnostic test for carpal tunnel syndrome. J Bone Joint Surg Am. 1991 Apr. 73(4):535-8. [Medline].
Gross PT, Tolomeo EA. Proximal median neuropathies. Neurol Clin. 1999 Aug. 17(3):425-45, v. [Medline].
Lama M. Carpal tunnel release in patients with negative neurophysiological examinations: clinical and surgical findings. Neurosurgery. 2009 Oct. 65(4 Suppl):A171-3. [Medline].
Levine BP, Jones JA, Burton RI. Nerve entrapments of the upper extremity: A surgical perspective. Neurol Clin. 1999 Aug. 17(3):549-65, vii. [Medline].
Morgan G, Wilbourn AJ. Cervical radiculopathy and coexisting distal entrapment neuropathies: double-crush syndromes?. Neurology. 1998 Jan. 50(1):78-83. [Medline].
Nuber GW, Assenmacher J, Bowen MK. Neurovascular problems in the forearm, wrist, and hand. Clin Sports Med. 1998 Jul. 17(3):585-610. [Medline].
Preston DC, Shefner JM, Rutkove SB. Electrodiagnosis of carpal tunnel syndrome: too many and too few tests. American Academy of Neurology Annual Meeting. 1999. 2PC003:
Preston DC. Distal median neuropathies. Neurol Clin. 1999 Aug. 17(3):407-24, v. [Medline].
Verdon ME. Overuse syndromes of the hand and wrist. Prim Care. 1996 Jun. 23(2):305-19. [Medline].
Zanette G, Cacciatori C, Tamburin S. Central sensitization in carpal tunnel syndrome with extraterritorial spread of sensory symptoms. Pain. 2010 Feb. 148(2):227-36. [Medline].
Friedhelm Sandbrink, MD Assistant Professor of Neurology, Georgetown University School of Medicine; Assistant Clinical Professor of Neurology, George Washington University School of Medicine and Health Sciences; Director, EMG Laboratory and Chief, Chronic Pain Clinic, Department of Neurology, Washington Veterans Affairs Medical Center
Disclosure: Nothing to disclose.
Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Received salary from Medscape for employment. for: Medscape.
Neil A Busis, MD Chief of Neurology and Director of Neurodiagnostic Laboratory, UPMC Shadyside; Clinical Professor of Neurology and Director of Community Neurology, Department of Neurology, University of Pittsburgh Physicians
Neil A Busis, MD is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine
Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: American Academy of Neurology<br/>Serve(d) as a speaker or a member of a speakers bureau for: American Academy of Neurology<br/>Received income in an amount equal to or greater than $250 from: American Academy of Neurology.
Nicholas Lorenzo, MD, MHA, CPE Co-Founder and Former Chief Publishing Officer, eMedicine and eMedicine Health, Founding Editor-in-Chief, eMedicine Neurology; Founder and Former Chairman and CEO, Pearlsreview; Founder and CEO/CMO, PHLT Consultants; Chief Medical Officer, MeMD Inc
Disclosure: Nothing to disclose.
Stephen A Berman, MD, PhD, MBA Professor of Neurology, University of Central Florida College of Medicine
Disclosure: Nothing to disclose.
Research & References of Median Neuropathy|A&C Accounting And Tax Services