Diabetic Polyneuropathy Is Associated With Pathomorphological Changes in Human Dorsal Root Ganglia: A Study Using 3T MR Neurography

Abstract

Diabetic neuropathy (DPN) is one of the most severe and yet most poorly understood complications of diabetes mellitus. In vivo imaging of dorsal root ganglia (DRG), a key structure for the understanding of DPN, has been restricted to animal studies. These have shown a correlation of decreased DRG volume with neuropathic symptom severity. Our objective was to investigate correlations of DRG morphology and signal characteristics at 3 Tesla (3T) magnetic resonance neurography (MRN) with clinical and serological data in diabetic patients with and without DPN. In this cross-sectional study, participants underwent 3T MRN of both L5 DRG using an isotropic 3D T2-weighted, fat-suppressed sequence with subsequent segmentation of DRG volume and analysis of normalized signal properties. Overall, 55 diabetes patients (66 ± 9 years; 32 men; 30 with DPN) took part in this study. DRG volume was smaller in patients with severe DPN when compared to patients with mild or moderate DPN (134.7 ± 21.86 vs 170.1 ± 49.22; p = 0.040). In DPN patients, DRG volume was negatively correlated with the neuropathy disability score (r = -0.43; 95%CI = -0.66 to -0.14; p = 0.02), a measure of neuropathy severity. DRG volume showed negative correlations with triglycerides (r = -0.40; 95%CI = -0.57 to -0.19; p = 0.006), and LDL cholesterol (r = -0.33; 95%CI = -0.51 to -0.11; p = 0.04). There was a strong positive correlation of normalized MR signal intensity (SI) with the neuropathy symptom score in the subgroup of patients with painful DPN (r = 0.80; 95%CI = 0.46 to 0.93; p = 0.005). DRG SI was positively correlated with HbA1c levels (r = 0.30; 95%CI = 0.09 to 0.50; p = 0.03) and the triglyceride/HDL ratio (r = 0.40; 95%CI = 0.19 to 0.57; p = 0.007). In this first in vivo study, we found DRG morphological degeneration and signal increase in correlation with neuropathy severity. This elucidates the potential importance of MR-based DRG assessments in studying structural and functional changes in DPN.

Keywords: diabetic polyneuropathy; dorsal root ganglion; magnetic resonance neurography; neuropathic pain; peripheral nervous system.

FIGURE 1

Process of patient recruitment and data acquisition.

FIGURE 2

Human dorsal root ganglia (DRG) segmentation. (A) Left and right L5 dorsal root ganglion on a T2–weighted, three–dimensional inversion recovery sequence with sampling perfection with application–optimized contrasts using different flip angle evolution. (B) Stacks of binarized masks of the left and right L5 dorsal root ganglion. (C) Three-dimensional reconstruction of DRG volume.

FIGURE 3

L5 dorsal root ganglion (DRG) volume and normalized signal intensity (SI) versus neuropathy disability score (NDS) and neuropathy symptom score (NSS). (A) Correlation of NDS and L5 DRG volume in patients with diabetic polyneuropathy [DPN; (r = –0.43; 95%CI = –0.66 to –0.14; p = 0.02)]. (B) DRG volumetry of a patient with a total L5 DRG volume of 277 mm³. (C) DRG volumetry of a patient with a total L5 DRG volume of 94 mm³. (D) Correlation of L5 DRG SI and NSS in painful DPN (r = 0.80; 95%CI = 0.46 to 0.93; p = 0.005). (E) L5 DRG SI in a patient with severe painful DPN (SI = 0.61 ± 0.094). (F) L5 DRG SI in a patient with mild painful DPN (SI = 0.45 ± 0.054).