The carpal tunnel is an anatomical structure surrounded by carpal bones and the transverse carpal ligament, serving as a narrow passageway through which the median nerve and nine flexor tendons pass. The volume of the carpal tunnel is approximately 5 cm³, which is relatively small, and even minor changes in internal pressure can significantly affect the median nerve [8] .

The transverse carpal ligament is a thick fibrous structure forming the roof of the carpal tunnel, connecting from the scaphoid tubercle and trapezium tubercle to the hamate and pisiform bones. It normally has a thickness of approximately 2 - 3 mm, but in carpal tunnel syndrome patients, it becomes thickened and loses elasticity [9] . The division of this ligament is the core of carpal tunnel release surgery, and anatomical studies have reported that complete division can increase the volume of the carpal tunnel by 30% - 40% [10] .

The median nerve is located most radially and superficially within the carpal tunnel, and branches cutaneous branches through the transverse carpal ligament for palmar skin innervation. Injury to this cutaneous branch is a major cause of postoperative scar pain, requiring careful dissection during surgery [11] . The thenar motor branch of the median nerve branches immediately after passing through the carpal tunnel and shows four anatomical variations according to Lanz’s classification [12] .

The nine flexor tendons within the carpal tunnel consist of four superficial digital flexor tendons, four deep digital flexor tendons, and one flexor pollicis longus tendon. These tendons are surrounded by synovium, and when inflammation or edema occurs, pressure within the carpal tunnel increases. Particularly, in systemic diseases such as diabetes mellitus, thyroid disease, and pregnancy, edema and thickening of tendon synovium occur, which can secondarily induce carpal tunnel syndrome [13] .

The vascular distribution of the carpal tunnel is important for understanding ischemic changes in the median nerve. The median nerve receives blood supply from the anterior interosseous artery and median artery, but vascular distribution is relatively poor in the carpal tunnel area. Sunderland reported that the vascular density of the median nerve within the carpal tunnel is 30% - 40% lower compared to proximal or distal areas, which is a factor that increases vulnerability to compression [14] .

Pressure within the carpal tunnel normally maintains 2 - 10 mmHg, but in carpal tunnel syndrome patients, it can increase to 30 - 110 mmHg. Particularly, pressure increases rapidly during wrist flexion or extension, which is the cause of nocturnal symptom exacerbation [15] . Gelberman et al. revealed that when pressure within the carpal tunnel increases above 30 mmHg, intraneural blood flow decreases significantly, and complete ischemia occurs above 50 mmHg [16] .

The median nerve plays an essential role in fine hand function. The sensory innervation area includes the thumb, index finger, middle finger, and radial half of the ring finger, which are the most important areas for pinch and grip functions. Motor innervation includes thenar muscles (opponens pollicis, abductor pollicis brevis, superficial head of flexor pollicis brevis), and dysfunction of these muscles seriously affects daily life [17] .

The conduction velocity of the median nerve is normally 50 - 60 m/s, but gradually decreases in carpal tunnel syndrome. In nerve conduction studies, sensory nerve conduction velocity delay appears earlier than motor nerve delay because sensory fibers are more sensitive to compression [18] . In severe cases, motor nerve conduction delay occurs along with thenar muscle atrophy, which is considered an irreversible change.

Changes in carpal tunnel pressure according to wrist joint position are closely related to symptom occurrence. Pressure is lowest in the neutral position and increases during flexion or extension. Particularly, pressure becomes maximum when the wrist is flexed 90 degrees, which is the pathophysiological basis of the Phalen test [19] . The reason symptoms worsen at night is also related to pressure increases due to abnormal wrist postures during sleep.

Changes in hand function in carpal tunnel syndrome cannot be explained simply by nerve compression alone. MacDermid et al. reported that in carpal tunnel syndrome patients, movement patterns and muscle activity of the wrist joint change, which is a factor that further deteriorates target function [20] . Particularly, greater force is used in pinch motions compared to normal individuals, creating a vicious cycle that further increases pressure within the carpal tunnel.

The pathophysiology of carpal tunnel syndrome is understood as a complex pathological process rather than simple mechanical compression. While the traditional compression theory explains nerve damage due to increased pressure within the carpal tunnel, recently the concept of multifactorial pathophysiology where ischemic changes, inflammatory reactions, and intraneural edema and fibrosis act in combination has become widely accepted [21] .

The pathophysiological process of carpal tunnel syndrome progresses through the following stages:

1) Initial compression and ischemic changes

When pressure within the carpal tunnel increases, perfusion pressure of capillaries within the median nerve decreases. Rydevik et al. in an experimental study reported that intraneural blood flow begins to decrease even at 8 mmHg pressure, and at 20 - 30 mmHg, venous return is blocked, causing intraneural edema [22] . These initial changes are reversible, but if persistent, they progress to structural changes.

2) Intraneural edema and inflammatory reaction

Persistent compression causes destruction of the blood-nerve barrier, resulting in intraneural edema. Edema further increases pressure within nerve fascicles, forming a vicious cycle. Jinrock et al. revealed that expression of inflammatory cytokines IL-1β and TNF-α in the median nerve of carpal tunnel syndrome patients increases 3 - 5 times compared to normal [23] .

3) Demyelination and axonal degeneration

Chronic compression and ischemia cause Schwann cell dysfunction, resulting in demyelination. Initially, focal demyelination appears, but if it progresses, it develops into axonal degeneration. At this stage, nerve conduction studies show conduction velocity delay along with amplitude reduction [24] .

4) Intraneural fibrosis and adhesion

Long-term compression induces fibrosis of the endoneurium and perineurium. This fibrosis limits nerve gliding and becomes a factor that hinders nerve function recovery even after compression is relieved. Guimberteau et al. reported that in chronic carpal tunnel syndrome, connective tissue around the median nerve becomes hypertrophied and adhesions form, affecting postoperative results [25] .

Molecular biological mechanisms of conservative treatment failure

Limitations of corticosteroid injection

Corticosteroid injection provides short-term symptom relief by suppressing inflammatory reactions but does not resolve the fundamental cause of compression. The 2024 AAOS guidelines state that there is strong evidence that corticosteroid injection does not provide long-term improvement [26] . Repeated steroid use can cause the following side effects:

First, tendon tissue weakening: Steroids injected around flexor tendons can suppress collagen synthesis in tendon tissue, increasing the risk of tendon rupture [27] .

Second, neurotoxicity: High concentrations of steroids can have direct neurotoxicity, and particularly particulate steroids such as betamethasone can cause serious nerve damage when injected intraneurally [28] .

Limitations of splint treatment

Splint wearing has the effect of reducing pressure within the carpal tunnel by fixing the wrist in a neutral position, but it does not resolve fundamental anatomical stenosis. Particularly, splint wearing alone cannot reverse already occurred intraneural edema and fibrosis, and its effect is limited in moderate or higher carpal tunnel syndrome [29] .

Mechanism of progressive nerve damage

Nerve damage can continue to progress even during conservative treatment. Bland in a long-term follow-up study reported that nerve conduction study findings deteriorated in approximately 60% of carpal tunnel syndrome patients receiving conservative treatment, and this progressed regardless of symptoms [30] . This suggests that fundamental nerve damage can continue to progress even when symptoms are stable.

Accurate assessment of patient symptoms and signs is the first step in diagnosis. Cases refractory to conservative treatment show the following characteristics:

The Boston Carpal Tunnel Questionnaire (BCTQ) is a standardized tool for objectively evaluating symptom severity and functional status. Surgical treatment should be considered when symptom severity scores are 3.0 or higher or functional status scores are 2.5 or higher [31] .

The diagnosis and severity of carpal tunnel syndrome can be evaluated through various special tests:

1) Phalen test: A test that checks whether numbness is induced in the median nerve distribution area when both wrists are maximally flexed and maintained for 1 minute. Sensitivity is reported as 68% and specificity as 73% [32] .

2) Tinel sign: A test that checks whether radiating numbness is induced to the median nerve distribution area when the median nerve pathway at the wrist is percussed.

3) Carpal compression test: A test that checks symptom induction by compressing the carpal tunnel area of the wrist for 30 seconds, which recent studies report as more sensitive than the Phalen test [33] .

4) Thumb opposition test: A test for evaluating thenar muscle function, which is a finding that appears in advanced cases.

Electrodiagnostic testing plays an important role in confirming the diagnosis of carpal tunnel syndrome and evaluating severity [34] .

Nerve conduction study: Measures sensory and motor nerve conduction velocities and latencies of the median nerve. In carpal tunnel syndrome, conduction velocity delay or amplitude reduction appears in the area crossing the carpal tunnel. It is judged abnormal when sensory nerve conduction delay is 3.5 ms or more or motor nerve distal latency is 4.2 ms or more.

Electromyography: The degree of axonal damage can be evaluated through electromyography of thenar muscles. In advanced cases, denervation findings and reinnervation findings can be confirmed.

Ultrasound examination: The degree of edema can be evaluated by measuring the cross-sectional area of the median nerve. When the cross-sectional area of the median nerve at the carpal tunnel entrance is 10 mm² or more, it suggests carpal tunnel syndrome [35] . Additionally, nerve gliding and thickness of the transverse carpal ligament can also be evaluated.

Magnetic resonance imaging (MRI): Signal intensity changes, edema, and changes in structures within the carpal tunnel of the median nerve can be observed, but it is not used for routine diagnosis and is mainly utilized for atypical cases or research purposes.

Surgical treatment is considered in the following cases:

Open carpal tunnel release is the most traditional and widely used surgical method.

Surgical technique: A 2 - 3 cm longitudinal incision is made in the palm to sequentially divide the skin, subcutaneous tissue, and palmar fascia, then completely divide the transverse carpal ligament under direct vision [36] .

Advantages:

Disadvantages:

Surgical results: Success rate is reported as 85% - 95%, with overall complication rate approximately 2% - 5% [37] .

Specific complications for open carpal tunnel release include:

Endoscopic carpal tunnel release is a minimally invasive surgical method introduced in the 1990s.

Surgical technique: A small incision (1 - 2 cm) is made at the wrist to insert an endoscope, and the transverse carpal ligament is divided under direct vision. There are single-port (Agee technique) and dual-port (Chow technique) methods [42] .

Advantages:

Disadvantages:

Surgical results: Success rate is similar to open surgery (90% - 95%), with better short-term functional results [43] .

Specific complications for endoscopic carpal tunnel release include:

A comprehensive meta-analysis by Zuo et al. reported that endoscopic carpal tunnel release shows superior results compared to open surgery in patient satisfaction (MD, 3.13; 95% CI, 1.43 - 4.82), key pinch strength (MD, 0.79 kg; 95% CI, 0.27 - 1.32), and return-to-work time (mean difference of 5.7 days earlier return) [49] . However, in long-term follow-up of 6 months or more, no clinically significant differences between the two methods were found.

Detailed criteria for surgical method selection:

Patient factors favoring endoscopic approach:

Patient factors favoring open approach:

Surgeon factors:

Ultrasound-guided carpal tunnel release

Recently, minimally invasive surgical techniques using ultrasound have been introduced. This method involves dividing the transverse carpal ligament using a special blade under real-time ultrasound guidance and received FDA approval in 2019 [51] .

Advantages:

Disadvantages:

Early studies report success rates of 85% - 90% with low complication rates, but longer follow-up studies are needed to establish efficacy compared to established techniques [52] .

Immediate postoperative (0 - 2 weeks):

Early recovery period (2 - 6 weeks):

Complete recovery period (6 - 12 weeks):

Long-term follow-up (3 - 6 months):

Predictive factors for successful surgical results:

Predictive factors for poor prognosis:

Overall complication rates:

Major complications (both techniques):

Causes of revision surgery:

Risk factors for revision surgery: Westenberg et al. reported that risk factors for revision surgery include male gender (OR 1.4), smoking (OR 1.8), diabetes (OR 1.6), and accompanying ulnar nerve entrapment syndrome (OR 2.1). Endoscopic surgery showed 2.96 times higher revision surgery risk compared to open surgery (95% CI 2.1 - 4.2) [56] .

Current literature limitations include:

Study heterogeneity: Significant variation in outcome measures across studies, with some using patient-reported outcomes while others focus on objective measures like grip strength or nerve conduction studies [57] .

Follow-up duration variability: Studies range from 6 months to 10 years follow-up, making long-term comparison difficult. Most studies report short-term outcomes (6 - 12 months) with limited long-term data [58] .

Patient selection bias: Many studies exclude patients with severe carpal tunnel syndrome, diabetes, or previous surgery, limiting generalizability to real-world practice [59] .

Surgeon experience variation: Few studies account for surgeon learning curve or experience level, which significantly affects outcomes, particularly for endoscopic techniques [60] .

Lack of standardized outcome measures: Absence of universally accepted outcome measures makes comparison between studies challenging. The need for validated, standardized assessment tools is critical [61] .