Microstructural changes of peripheral nerves in early multiple sclerosis: A prospective magnetic resonance neurography study

Background and purpose: Multiple sclerosis (MS) is a demyelinating disorder of the central nervous system (CNS). However, there is increasing evidence of peripheral nerve involvement. This study aims to characterize the pattern of peripheral nerve changes in patients with newly diagnosed MS using quantitative magnetic resonance (MR) neurography.Methods: In this prospective study, 25 patients first diagnosed with MS according to the revised McDonald criteria (16 female, mean age = 32.8 +/- 10.6 years) and 14 healthy controls were examined with high-resolution 3-T MR neurography of the sciatic nerve using diffusion kurtosis imaging (DKI; 20 diffusional directions, b = 0, 700, 1200 s/mm(2)) and magnetization transfer imaging (MTI). In total, 15 quantitative MR biomarkers were analyzed and correlated with clinical symptoms, intrathecal immunoglobulin synthesis, electrophysiology, and lesion load on brain and spine MR imaging.Results: Patients showed decreased fractional anisotropy (mean = 0.51 +/- 0.04 vs. 0.56 +/- 0.03, p < 0.001), extra-axonal tortuosity (mean = 2.32 +/- 0.17 vs. 2.49 +/- 0.17, p = 0.008), and radial kurtosis (mean = 1.40 +/- 0.23 vs. 1.62 +/- 0.23, p = 0.014) and higher radial diffusivity (mean = 1.09 center dot 10(-3) mm(2)/s +/- 0.16 vs. 0.98 +/- 0.11 center dot 10(-3) mm(2)/s, p = 0.036) than controls. Groups did not differ in MTI. No significant association was found between MR neurography markers and clinical/laboratory parameters or CNS lesion load.Conclusions: This study provides further evidence of peripheral nerve involvement in MS already at initial diagnosis. The characteristic pattern of DKI parameters indicates predominant demyelination and suggests a primary coaffection of the peripheral nervous system in MS. This first human study using DKI for peripheral nerves shows its potential and clinical feasibility in providing novel biomarkers.