Quantification and Proximal-to-Distal Distribution Pattern of Tibial Nerve Lesions in Relapsing-Remitting Multiple Sclerosis

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 (T2app)), 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 T2app and an increase in ρ compared to controls (T2app thigh: p < 0.0001, T2app 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 T2app and T2-signal, but not for ρ. Conclusion PNS involvement in RRMS is characterized by a decrease in T2app 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.

Multiparametric Quantitative MRI of Peripheral Nerves in the Leg: A Reliability Study

“…Length‐dependent changes of peripheral nerve qMRI parameters were previously reported in patients with polyneuropathies 8,31 and multiple sclerosis 37 . In this study, MTsat distal‐to‐proximal increases were observed in healthy volunteers.…”

“…Length-dependent changes of peripheral nerve qMRI parameters were previously reported in patients with polyneuropathies 8,31 and multiple sclerosis. 37 In this study, MTsat distal-to-proximal increases were observed in healthy volunteers. Presumably, the MTsat minimizes sensitivities to T 1 and radiofrequency field inhomogeneities by decompiling the two parameters.…”

Peripheral nerve involvement in hereditary spastic paraplegia characterized by quantitative magnetic resonance neurography

“…Importantly, we found group differences in MRN markers either solely or with higher significance levels at the lower leg, suggesting that peripheral nerve involvement occurs predominantly at the lower leg. This finding in HSP is unique among the diffuse neuropathies characterized by MRN to date, as a proximal rather than a distal dominant MRN marker change was described in other entities [12–14, 20–22, 25]. Furthermore, the presumably distal predominance of microstructural changes in the extracellular nerve matrix might explain our finding that MTR (measured only at the thigh) failed to detect nerve involvement in SPG4 PNP−, even though it previously showed superiority in identifying subclinical nerve damage in other neuropathies.…”

“…However, contrary to previous observations in SMA, a reactive, potentially edema‐induced increase of nerve T2 app was absent in SCA3 and HSP. Histopathologic and MRN studies conducted in MS revealed that areas of demyelination in the brain as well as PNS lesions correlate with an increase in ρ [18, 25, 27]. Consequently, the observed decrease in nerve ρ in HSP argues against a relevant demyelination in SPG4 and SPG7, which would rather point towards mimicking immunologic or neurometabolic diseases.…”

“…In detail, distal-symmetric PNPs of different etiologies, such as hereditary or systemic amyloidosis, diabetes, or alcohol dependency, are characterized by an early, often subclinical increase of ρ, followed by an additional T2 app increase in symptomatic or more advanced PNP stages [12,13,20,22]. In the demyelinating disease multiple sclerosis (MS), peripheral nerve involvement is characterized by a similar increase in ρ, while T2 app is reduced [18,25]. In the motor neuron disease 5q-linked spinal muscular atrophy (SMA) another unique alteration of MRN markers was observed with a decrease in ρ (and CSA), likely representing the axonal loss induced by a decay of lower motor neurons, and an increase in T2 app potentially caused by reactive nerve edema [11].…”