Quantification and Proximal-to-Distal Distribution Pattern of Tibial Nerve Lesions in Relapsing-Remitting Multiple Sclerosis : Assessment by MR Neurography

Abstract

Purpose: Recent studies suggest an involvement of the peripheral nervous system (PNS) in multiple sclerosis (MS). Here, we characterize the proximal-to-distal distribution pattern of peripheral nerve lesions in relapsing-remitting MS (RRMS) by quantitative magnetic resonance neurography (MRN).

Methods: A total of 35 patients with RRMS were prospectively included and underwent detailed neurologic and electrophysiologic examinations. Additionally, 30 age- and sex-matched healthy controls were recruited. 3T MRN with anatomical coverage from the proximal thigh down to the tibiotalar joint was conducted using dual-echo 2‑dimensional relaxometry sequences with spectral fat saturation. Quantification of PNS involvement was performed by evaluating microstructural (proton spin density (ρ), T2-relaxation time (T2_app)), and morphometric (cross-sectional area, CSA) MRN markers in every axial slice.

Results: In patients with RRMS, tibial nerve lesions at the thigh and the lower leg were characterized by a decrease in T2_app and an increase in ρ compared to controls (T2_app thigh: p < 0.0001, T2_app lower leg: p = 0.0040; ρ thigh: p < 0.0001; ρ lower leg: p = 0.0098). An additional increase in nerve CSA was only detectable at the thigh, while the semi-quantitative marker T2w-signal was not altered in RRMS in both locations. A slight proximal-to-distal gradient was observed for T2_app and T2-signal, but not for ρ.

Conclusion: PNS involvement in RRMS is characterized by a decrease in T2_app and an increase in ρ, occurring with proximal predominance at the thigh and the lower leg. Our results indicate microstructural alterations in the extracellular matrix of peripheral nerves in RRMS and may contribute to a better understanding of the pathophysiologic relevance of PNS involvement.

Keywords: Magnetic resonance neurography; Peripheral nervous system; Proton spin density; Quantitative imaging markers; T2-relaxometry.

Fig. 1

Quantitative microstructural MRN markers. Nerve T2_app (a, b) and nerve ρ (c, d) mean values at the thigh (a, c) and at the lower leg (b, d) were plotted separately for controls and RRMS in a box and whisker plot. Both microstructural markers differentiated well between RRMS patients and healthy controls when measured at the thigh and also at the lower leg. Significant differences are indicated by respective p values. a.u. arbitrary units, ρ proton spin density, RRMS relapsing-remitting multiple sclerosis, T2_app apparent T2-relaxation time

Fig. 2

Semi-quantitative T2w signal and quantitative morphometric MRN markers. Nerve T2w signal (a, b) and nerve CSA (c, d) mean values at the thigh (a, c) and at the lower leg (b, d) were plotted separately for controls and RRMS in a box and whisker plot. While nerve T2w signal did not separate between RRMS patients and healthy controls, nerve CSA was higher in RRMS than in controls, but only when measured at the thigh and not at the lower leg. Significant differences are indicated by respective p values. CSA cross-sectional area, RRMS relapsing-remitting multiple sclerosis

Fig. 3

MRN source images. Representative magnetic resonance neurography (MRN) images (axial dual-echo turbo spin echo relaxometry sequences with spectral fat saturation) at the left proximal thigh (a, b), distal thigh (c, d), proximal lower leg (e, f), and distal lower leg (g, h) are shown at equal slice positions in a healthy control (left: a, c, e, g) and a patient with relapsing-remitting multiple sclerosis (right: b, d, f, h). Details show the segmented tibial fascicles within the sciatic nerve (a–d) and their distal continuation as tibial nerve (e–h). Note the diffuse, heterogeneous, and hyperintense lesion distribution in RRMS compared to the control. In RRMS, nerve CSA was also higher at the proximal and distal thigh, but not at the lower leg