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

Mojaddidi, Moaz A.; Ahmed, Mohammed S.; Ali, Razwan; Jeziorska, Maria; Al-Sunni, Ahmed; Thomsen, Niels LU ; Dahlin, Lars LU and Malik, Rayaz A. (2014) In Diabetologia 57(8). p.1711-1719
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Carpal tunnel syndrome, Diabetes, HIF-1 alpha, Microangiopathy, Myelinated fibre, Neuropathy, Unmyelinated fibre, VEGF
in
Diabetologia
volume
57
issue
8
pages
1711 - 1719
publisher
Springer Verlag
external identifiers
  • wos:000338997500022
  • scopus:84904737844
ISSN
1432-0428
DOI
10.1007/s00125-014-3271-3
language
English
LU publication?
yes
id
e07daeaf-132e-409f-a29b-295cc638b401 (old id 4591828)
date added to LUP
2014-09-04 14:56:38
date last changed
2017-06-18 03:01:55
@article{e07daeaf-132e-409f-a29b-295cc638b401,
  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 &lt; 0.05 vs non-diabetic patients), PIN myelinated fibre density (p &lt; 0.05), fibre area (p &lt; 0.0001) and axon area (p &lt; 0.0001) were reduced, the percentage of unassociated Schwann cell profiles (p &lt; 0.0001) and unmyelinated axon density (p &lt; 0.0001) were increased and the axon diameter was reduced (p &lt; 0.0001). Endoneurial capillary basement membrane area was increased (p &lt; 0.0001) in diabetic patients, but endothelial cell number was increased (p &lt; 0.01) and luminal area was reduced (p &lt; 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 &lt; 0.05) and its receptors VEGFR-1 (p &lt; 0.01) and VEGFR-2 (p &lt; 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.},
  author       = {Mojaddidi, Moaz A. and Ahmed, Mohammed S. and Ali, Razwan and Jeziorska, Maria and Al-Sunni, Ahmed and Thomsen, Niels and Dahlin, Lars and Malik, Rayaz A.},
  issn         = {1432-0428},
  keyword      = {Carpal tunnel syndrome,Diabetes,HIF-1 alpha,Microangiopathy,Myelinated fibre,Neuropathy,Unmyelinated fibre,VEGF},
  language     = {eng},
  number       = {8},
  pages        = {1711--1719},
  publisher    = {Springer Verlag},
  series       = {Diabetologia},
  title        = {Molecular and pathological studies in the posterior interosseous nerve of diabetic and non-diabetic patients with carpal tunnel syndrome},
  url          = {http://dx.doi.org/10.1007/s00125-014-3271-3},
  volume       = {57},
  year         = {2014},
}