Molecular and pathological studies in the posterior interosseous nerve of diabetic and non-diabetic patients with carpal tunnel syndrome

Moaz A. Mojaddidi, Mohammed S. Ahmed, Razwan Ali, Maria Jeziorska, Ahmed Al-Sunni, Niels Thomsen, Lars Dahlin, Rayaz A. Malik

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Abstract

Aims/hypothesis We sought to establish the molecular and pathological changes predisposing diabetic and non-diabetic patients to the development of carpal tunnel syndrome (CTS). Methods The posterior interosseous nerve (PIN) was biopsied in 25 diabetic and 19 non-diabetic patients undergoing carpal tunnel decompression for CTS. Detailed morphometric and immunohistological analyses were performed in the nerve biopsy. Results In diabetic patients median nerve distal motor latency was prolonged (p < 0.05 vs non-diabetic patients), PIN myelinated fibre density (p < 0.05), fibre area (p < 0.0001) and axon area (p < 0.0001) were reduced, the percentage of unassociated Schwann cell profiles (p < 0.0001) and unmyelinated axon density (p < 0.0001) were increased and the axon diameter was reduced (p < 0.0001). Endoneurial capillary basement membrane area was increased (p < 0.0001) in diabetic patients, but endothelial cell number was increased (p < 0.01) and luminal area was reduced (p < 0.05) in non-diabetic patients with CTS. There was no difference in the expression of hypoxia-inducible factor 1 alpha between diabetic and non-diabetic patients with CTS. However, the expression of vascular endothelial growth factor A (VEGF) (p < 0.05) and its receptors VEGFR-1 (p < 0.01) and VEGFR-2 (p < 0.05) was significantly increased in diabetic patients, particularly those with type 1 diabetes, and related to the severity of nerve fibre pathology. Conclusions/interpretation This study demonstrates increased nerve fibre and microvascular pathology in relation to enhanced expression of VEGF and its receptors in a non-compressed nerve in diabetic compared with non-diabetic patients with CTS. It therefore provides a potential molecular and pathological basis for the predisposition of diabetic patients to the development of CTS.
Original languageEnglish
Pages (from-to)1711-1719
JournalDiabetologia
Volume57
Issue number8
DOIs
Publication statusPublished - 2014

Subject classification (UKÄ)

  • Endocrinology and Diabetes

Keywords

  • Carpal tunnel syndrome
  • Diabetes
  • HIF-1 alpha
  • Microangiopathy
  • Myelinated fibre
  • Neuropathy
  • Unmyelinated fibre
  • VEGF

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