Validation of the nerve axon reflex for the assessment of small nerve fibre dysfunction

Objective: To validate nerve-axon reflex-related vasodilatation as an objective method to evaluate C-nociceptive fibre function by comparing it with the standard diagnostic criteria. Methods: Neuropathy was evaluated in 41 patients with diabetes (26 men and 15 women) without peripheral vascular disease by assessing the Neuropathy Symptom Score, the Neuropathy Disability Score (NDS), the vibration perception threshold (VPT), the heat detection threshold (HDT), nerve conduction parameters and standard cardiovascular tests. The neurovascular response to 1% acetylcholine (Ach) iontophoresis was measured at the forearm and at both feet by laser flowmetry. An age-matched and sex-matched control group of 10 healthy people was also included. Results: Significant correlations were observed between the neurovascular response at the foot and HDT (r(s) = -0.658; p < 0.0001), NDS (r(s) = -0.665; p < 0.0001), VPT (r(s) = -0.548; p = 0.0005), tibial nerve conduction velocity (r(s) = 0.631; p = 0.0002), sural nerve amplitude (r(s) = 0.581; p = 0.0002) and autonomic function tests. According to the NDS, in patients with diabetes who had mild, moderate or severe neuropathy, a significantly lower neurovascular response was seen at the foot than in patients without neuropathy and controls. A neurovascular response < 50% was found to be highly sensitive (90%), with a good specificity (74%), in identifying patients with diabetic neuropathy. Conclusion: Small-fibre dysfunction can be diagnosed reliably with neurovascular response assessment. This response is already reduced in the early stages of peripheral neuropathy, supporting the hypothesis that small-fibre impairment is an early event in the natural history of diabetic neuropathy.