Sural nerve pathology in diabetic patients with minimal but progressive neuropathy

Aims/hypothesis: The early pathological features of human diabetic neuropathy are not clearly defined. Therefore we quantified nerve fibre and microvascular pathology in sural nerve biopsies from diabetic patients with minimal neuropathy. Methods: Twelve diabetic patients underwent detailed assessment of neuropathy and fascicular sural nerve biopsy at baseline, with repeat assessment of neuropathy 8.7 +/- 0.6 years later. Results: At baseline, neuropathic symptoms, neurological deficits, quantitative sensory testing, cardiac autonomic function and peripheral nerve electrophysiology showed minimal abnormality, which deteriorated at follow-up. Myelinated fibre density, fibre and axonal area, and g-ratio were normal but teased fibre studies showed paranodal abnormalities (p < 0.001), segmental demyelination (p < 0.01) and remyelination (p < 0.01) without axonal degeneration. Unassociated Schwann cell profile density (p < 0.04) and unmyelinated axon density (p < 0.001) were increased and axon diameter was decreased (p < 0.007). Endoneurial capillaries demonstrated basement membrane thickening (p < 0.006), endothelial cell hyperplasia (p < 0.004) and a reduction in luminal area (p < 0.007). Conclusions/interpretation: The early pathological features of human diabetic neuropathy include an abnormality of the myelinated fibre Schwann cell and unmyelinated fibre degeneration with regeneration. These changes are accompanied by a significant endoneurial microangiopathy.