What is the pathophysiology of carpal tunnel syndrome (CTS)?

Pathophysiology of Carpal Tunnel Syndrome

Carpal tunnel syndrome (CTS) is primarily caused by compression of the median nerve as it travels through the carpal tunnel at the wrist, resulting from a combination of mechanical trauma, increased pressure, and ischemic damage to the nerve. 1, 2

Core Pathophysiological Mechanisms

Mechanical Factors

• The median nerve becomes compressed within the confined space of the carpal tunnel
• This compression occurs between the carpal bones and the transverse carpal ligament
• Mechanical trauma leads to nerve fiber injury and demyelination 3
• Repetitive wrist movements and vibration exposure contribute to mechanical stress on the nerve 4

Pressure-Related Changes

• Elevated carpal tunnel pressure is a key factor in pathogenesis
• Normal carpal tunnel pressure: 2-10 mmHg
• In CTS patients, pressure can rise to 30+ mmHg, especially with wrist flexion or extension 2
• Increased pressure leads to:
  • Impaired microcirculation within the nerve
  • Edema formation
  • Further compression in the confined space 3, 2

Ischemic Damage

• Compression causes reduced blood flow to the median nerve
• Ischemia leads to:
  • Impaired axonal transport
  • Nerve fiber dysfunction
  • If prolonged, permanent nerve damage 3, 1
• The cycle of ischemia and reperfusion may cause oxidative stress and further nerve damage 2

Pathophysiological Progression

1. Initial Phase: Intermittent mechanical compression and ischemia

   • Temporary symptoms that resolve with position change
   • Reversible nerve conduction changes 3

2. Intermediate Phase: Persistent compression

   • Demyelination of nerve fibers
   • Slowing of nerve conduction velocity
   • More consistent symptoms 1, 2

3. Advanced Phase: Chronic compression

   • Axonal degeneration
   • Thenar muscle atrophy (late finding)
   • Permanent sensory and motor deficits 4, 5

Diagnostic Correlations with Pathophysiology

• Ultrasound can identify median nerve enlargement (cross-sectional area >15 mm² is diagnostic) 4
• Nerve conduction studies reflect the pathophysiological changes:
  • Mild CTS: Sensory abnormalities only
  • Moderate CTS: Both sensory and motor abnormalities
  • Severe CTS: Axonal loss with reduced amplitudes and/or denervation on EMG 4

Common Pitfalls in Understanding CTS Pathophysiology

• Failing to recognize that symptoms may not correlate with severity of nerve damage
• Overlooking concurrent compression at multiple sites (double crush syndrome)
• Approximately 6% of CTS cases have concurrent pronator syndrome 4
• Misattributing symptoms to CTS when they may be due to cervical radiculopathy or other conditions 4
• Not recognizing that normal nerve conduction studies do not necessarily exclude CTS, as intermittent compression may not always be detected during testing 5

Risk Factors That Contribute to Pathophysiology

• Conditions that increase fluid retention (pregnancy, hypothyroidism)
• Inflammatory conditions (rheumatoid arthritis, tenosynovitis)
• Anatomical variants that reduce carpal tunnel space
• Obesity (increases fat deposition within the carpal tunnel)
• Repetitive wrist movements and vibration exposure 1, 2

Understanding the pathophysiology of CTS is essential for appropriate diagnosis and treatment selection, with management strategies targeting the underlying mechanisms of nerve compression and inflammation.