title: Molecular and pathological studies in the posterior interosseous nerve of diabetic and non-diabetic patients with carpal tunnel syndrome.
abstract: OBJECTIVE
  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 1α 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
  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.
authors.affiliation: Centre for Endocrinology and Diabetes, Institute of Human Development, Faculty of Medical and Human Sciences, The University of Manchester, AV Hill Building, Oxford Road, Manchester, M13 9PT, UK.
authors.forename: Moaz A
authors.initials: MA
authors.lastname: Mojaddidi
authors.forename: Mohammed S
authors.initials: MS
authors.lastname: Ahmed
authors.forename: Razwan
authors.initials: R
authors.lastname: Ali
authors.forename: Maria
authors.initials: M
authors.lastname: Jeziorska
authors.forename: Ahmed
authors.initials: A
authors.lastname: Al-Sunni
authors.forename: Niels O B
authors.initials: NO
authors.lastname: Thomsen
authors.forename: Lars B
authors.initials: LB
authors.lastname: Dahlin
authors.forename: Rayaz A
authors.initials: RA
authors.lastname: Malik
mesh_terms: D000328:Adult; D000368:Aged; D002349:Carpal Tunnel Syndrome / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D003929:Diabetic Neuropathies / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008297:Male; D008475:Median Nerve / Q000378:metabolism / Q000503:physiopathology; D008875:Middle Aged; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1