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Carpal Tunnel Syndrome Results from Persistent Hypoxia and Senescence Within the Wrist Flexor Tenosynovium
Sebastian D Arango, B.S.
1; Jacob Zeitlin, BS
2; A Lee Osterman, MD
2; Michael Weinik, DO
2; Rowena McBeath, MD
31Philadelphia Hand to Shoulder Center - Thomas Jefferson University, Philadelphia, PA; 2Philadelphia Hand to Shoulder Center, Philadelphia, PA; 3The Philadelphia Hand Center, Thomas Jefferson University, Philadelphia, PA
Hypothesis: Carpal Tunnel Syndrome (CTS), a prevalent and incapacitating condition resulting from repetitive activity over time, manifests as hand pain, numbness, and tingling exacerbated by repeated wrist flexion. Although CTS is a compressive neurapraxia, the physiologic mechanism responsible – either direct compression of the nerve itself or the effects of compression on the tenosynovial vascular supply to the nerve over time – is unclear. We believe that CTS results from a hypoxic tenosynovial environment due to compression of the tenosynovial vasculature over time. To this end, we identified patients presenting with symptoms consistent with CTS and hypothesized that those patients presenting with moderate-severe CTS display increased tenosynovial hypertrophy, as detected via ultrasound, and altered molecular markers of hypoxia and senescence as detected via immunohistochemistry of wrist flexor tenosynovium at the time of surgery.
Methods: 26 patients (age 45-72) with moderate-severe CTS as determined via EMG/NCS (DSL>4.5, DML>5.5) were evaluated using ultrasound and the tenosynovial thickness measured at the location of the pronator quadratus and the distal carpal tunnel according to established guidelines
2. Tenosynovial tissue samples from these patients were collected at the time of carpal tunnel release via a mini-open approach (IRB#13D.238) and examined using immunohistochemistry for collagen 1, collagen 3, aggrecan, HIF1a (hypoxia inducible-factor 1a, activated in response to hypoxia), and p16 (a marker of cell senescence).
Results: Patients with moderate-severe CTS as determined via pre-operative EMG/NCS and ultrasound demonstrated increased wrist flexor tenosynovial hypertrophy as compared to normal controls (p<0.05). Tenosynovium from these patients revealed increased aggrecan, HIF1a and p16 as compared to normal controls via immunohistochemical analysis (Figure 1).
Summary Points:
- Carpal tunnel syndrome is a compression neuropathy. We propose that median nerve compression results from wrist flexor tenosynovial hypertrophy, which correlates with worsening neuropathic symptoms and age.
- Ultrasound-detected tenosynovial hypertrophy is associated with worsening neuropathic symptoms and age.
- Immunohistochemical examination of tenosynovium from patients undergoing carpal tunnel release for moderate-severe CTS demonstrated increased HIF1a activity and senescence markers, suggesting age-related changes in tenosynovial vascularity contribute to worsening symptoms.
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