Improving Microcirculation With Nerve Decompression: The Missing Link in Treatment of Diabetic Neuropathy and Diabetic Foot Ulcer

Abstract

Sympathetic dysfunction in skin is well known in diabetic peripheral neuropathy. This produces dry, cracked, peeling skin susceptible to infection and also epidermal microcirculation insufficiency. Impaired autonomic neurovascular control opens dermal arterio-venous anastomoses and shunts microcirculation away from the epidermis and impairs skin oxygenation and nutrition. Few recognise that diabetic neuropathy includes swelling-induced entrapment neuropathy. Multiple peripheral nerves, swollen by the secondary polyol metabolic pathway, suffer local compressions at fibro-osseous tunnels. This includes the C-fibres controlling autonomic functions which constitute most of the nerve axons. No current standard of care therapy addresses the sympathetic-regulated neurovascular impairment of skin microcirculation in diabetes. Epineurolysis surgery for peripheral nerve decompression relieves local axonal compressions and generates recovery of sub-epidermal capillary flow. Clinical and animal diabetes studies have demonstrated objective improvements to epidermal hypoxia, demyelination and axonal histology. Seven surgery studies find an average 1.39% recurrence and zero amputations after prior Risk Class 3 wound healing in a mean of 1.78 years of follow-up. Deficits of electrophysiology, transcutaneous oxygenation and vasa nervorum circulation also improve. Surgically improved microcirculation is physiology-based. Nerve decompression minimises diabetic peripheral neuropathy, avoids initial diabetic foot ulcers, promotes neuropathic diabetic foot ulcer healing and minimises ulcer recurrences and subsequent amputation. The observational studies of these important benefits suggest wide application to the complications of diabetes neuropathy and beg for academic attention to Level 1 EBM confirmation.

Keywords: amputation in diabetes; autonomic neuropathy; entrapment neuropathy; skin microcirculation; surgery.

FIGURE 1

(A) Illustration of the epidermal and dermal circulation; (B) The altered blood flow pattern in diabetes. With sympathetic paralysis, Increased flow through the a‐v anastomosis shunts blood directly into the venous outflow. Combined with a pre‐capillary constriction, this robs the epidermis of oxygenation and nutrition [7]. With permission from Lectorio (A), and Prof. Bengt Fagrell and Prof. Gun Jorneskog (B).

FIGURE 2

Quantitative example showing deficient epidermal blood flow (red) in diabetic neuropathy subjects in comparison with normal pressure‐induced vasodilation (blue). With permission from Zwanenberg [14].

FIGURE 3

An operative photograph after release of the medial retinaculum at the tibial malleolus in a diabetic patient demonstrates the enlargement and edematous appearance of the posterior tibial nerve where it separates into medial calcaneal, medial plantar and lateral plantar nerves. Courtesy of Ryan Pereira, DPM.

FIGURE 4

DPN is often described as a length dependent axonopathy resulting from a dysfunctional metabolic pathway shown on the left. The polyol pathway, shown on the right, is also well‐known and results in an increased concentration of fructose and sorbitol within the nerve and myelin. This results in hyperosmotic swelling of the nerve and entrapment neuropathy (EN) at several fibro‐osseous tunnels in the lower extremities. EN can explain both the sensorimotor and autonomic deficits seen with DPN including dermal a‐v shunting, CCI, and diminished PIV, which can all be improved with nerve decompression.

FIGURE 5

(A) In the healthy nerve water and glucose equilibrate across the axonal membrane bidirectionally by diffusion and/or transport. (B) In diabetes, hyperglycaemia drives the polyol metabolic path to accumulate sorbitol and fructose. (C) Sorbitol and fructose have no membrane transporters and accumulate inside the axon. Water or tissue fluid is drawn across the membrane into the axons to equalise osmolarity. (D) This causes a swelling of the myelin sheath, axons, fascicles and nerve diameters. The healthy nerve glides easily through the fibro‐osseous tunnel (A) while the swollen nerve suffers measurable compression (D).