Comparison of Immunohistochemical and Histopathological Findings between Patients with Diabetic and Idiopathic Carpal Tunnel Syndrome

<b>Background:</b> Carpal tunnel syndrome (CTS) is the most common nerve entrapment syndrome, caused by median nerve compression at the wrist. Its aetiology remains unclear, with idiopathic and diabetic-related forms. Diabetic patients (type 1 and 2) have a higher CTS risk, likely due to oedema, neo-angiogenesis and increased non-inflammatory fibrosis in the sub-synovial connective tissue (SSCT). Vascular endothelial growth factor (VEGF) A plays a key role in vascular permeability and angiogenesis, particularly in diabetic CTS. This study compared histopathological differences and VEGF expression in idiopathic and diabetic CTS. <b>Methods:</b> A total of 45 CTS patients were divided into three groups: idiopathic CTS (CTS-I, <i>n</i> = 15), type 1 diabetic CTS (CTS-DM1, <i>n</i> = 15) and type 2 diabetic CTS (CTS-DM2, <i>n</i> = 15). Biopsy specimens from the transverse ligament, tenosynovium and epineurium were analysed for fibrosis, oedema, vascular proliferation and vascular thickness. Immunohistochemistry assessed VEGF-A and its receptors VEGFR-1 and VEGFR-2. <b>Results:</b> Vascular proliferation and thickness were higher in CTS-DM1 than in CTS-I (<i>p</i> < 0.01) and CTS-DM2 (<i>p</i> < 0.05). Tenosynovium in CTS-DM1 and CTS-DM2 showed increased oedema, vascular proliferation and thickness compared to CTS-I (<i>p</i> < 0.001). Epineurium showed no significant oedema differences but had increased vascular proliferation and thickness in diabetic CTS (<i>p</i> < 0.001). VEGF and its receptors were significantly overexpressed in fibroblasts, endothelial and synovial cells in diabetic CTS. <b>Conclusions:</b> Our study evidenced an increased expression of VEGF and its receptors 1 and 2 in endothelial cells, fibroblasts and synovial cells of the transverse ligament, tenosynovium and epineurium in patients with diabetic CTS compared to idiopathic CTS. We also observed increased oedema, vascular proliferation, vascular wall thickness and tenosynovial fibrosis in diabetic patients. These histological findings are known to be promoted by VEGF and may provide a potential pathophysiological basis for CTS. These findings suggest a therapeutic rationale for anti-VEGF therapy as an adjunct or alternative to surgery in diabetic CTS patients. <b>Level of Evidence:</b> Level III (Diagnostic).