The feasibility of contact heat evoked potentials (CHEPs) in early detection of symptomatic diabetic distal symmetric polyneuropathy (DSP)

Abstract

Background: DSP is a common complication in diabetes, yet treatment for it has been disappointing. This may be because treatments typically target reducing pain rather than reducing nerve damage. Methods to identify types of nerve damage are available but too sophisticated and specialized. Therefore, quick, convenient, inexpensive method that can be used to identify type of nerve damage in patients suffering from DSP is needed. Objective: To investigate the feasibility of using contact heat evoked potentials (CHEPs) as a detection tool for DSP. Method: This study had 3 stages. 1st stage: The first stage was a systematic review of studies that have been published on the treatment effect of pain in diabetic neuropathy. Randomised controlled trials comparing topically and orally administered drugs with a placebo in adults with painful diabetic neuropathy were included. The primary outcome was dichotomous data for 50% or moderate pain reduction. 2nd stage: The second stage was a cross-sectional study testing the reliability of CHEPs. Twenty-two healthy adults were recruited. CHEPs were recorded using a 64-channel EEG cap. The peak stimulating temperature was 51°C. Two separate blocks of thermal stimulations were applied to dorsum of foot and 10cm proximal to lateral malleolus. 3rd stage: The third stage was a cross-sectional study. Thirteen healthy adults, 19 diabetic patients and 10 diabetic patients with lower limb symptoms were recruited. CHEPs were recorded at midline channels of healthy adults, and of diabetic patients with and without lower limb symptoms. The peak stimulating temperature of 51°C was applied to dorsum of foot and 10cm proximal to lateral malleolus. Results: 1st stage: Of the 31 relevant reports found, 25 reports were included and seven were excluded. Nearly 50% of patients with diabetic neuropathy had un-resolved pain when the treatment focused on pain intensity reduction. The effects of different classes of medications on particular damaged nerve are not known. 2nd stage: The Cronbach's alpha for first negative peak - first positive peak amplitude (N1-P1 amplitude) were 0.901 and 0.753 with stimulation of dorsum of foot and 10cm proximal to lateral malleolus respectively. The single measure intra-class coefficients for N1-P1 amplitude were 0.802 and 0.604 for stimulation of dorsum of foot and 10cm proximal to lateral malleolus respectively. 3rd stage: There was significant difference of N1-P1 amplitude among the three groups following stimulation of dorsum of foot (p = 0.028) and 10cm proximal to lateral malleolus (p = 0.006). Post hoc analysis showed that N1-P1 amplitude was significantly lower in diabetic patients with lower limb symptoms when compared to diabetic patients (p = 0.006) and healthy controls (p = 0.014) with stimulation of 10cm proximal to lateral malleolus. Discussion: There may be loss of Aδ nerve fibres in diabetic patients with lower limb symptoms as reflected by significant reduction in the N1-P1 amplitudes of CHEPs. The results were consistent with morphological studies on nerves of diabetic patients with DSP; these studies have reported markedly reduction in intraepidermal nerve fibres density, a gold standard for diagnosing small fibre neuropathy, has been reported. Conclusion: The treatment effects on reducing nerve damage in patients with painful DSP were not known. CHEPs are a reliable method for assessing the integrity of Aδ nerve fibres. Early identification of Aδ nerve fibres damage in DSP by CHEPs is feasible.