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Here, we characterize the proximal-to-distal distribution pattern of peripheral nerve lesions in relapsing-remitting MS (RRMS) by quantitative magnetic resonance neurography (MRN).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>A total of 35\u00a0patients with RRMS were prospectively included and underwent detailed neurologic and electrophysiologic examinations. Additionally, 30\u00a0age- and sex-matched healthy controls were recruited. 3T\u00a0MRN with anatomical coverage from the proximal thigh down to the tibiotalar joint was conducted using dual-echo 2\u2011dimensional relaxometry sequences with spectral fat saturation. Quantification of PNS involvement was performed by evaluating microstructural (proton spin density\u00a0(\u03c1), T2-relaxation time (T2<jats:sub>app<\/jats:sub>)), and morphometric (cross-sectional area, CSA) MRN markers in every axial slice.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>In patients with RRMS, tibial nerve lesions at the thigh and the lower leg were characterized by a\u00a0decrease in T2<jats:sub>app<\/jats:sub> and an increase in\u00a0\u03c1 compared to controls (T2<jats:sub>app<\/jats:sub> thigh: <jats:italic>p<\/jats:italic>\u202f&lt;\u20090.0001, T2<jats:sub>app<\/jats:sub> lower leg: <jats:italic>p<\/jats:italic>\u202f=\u20090.0040; \u03c1\u00a0thigh: <jats:italic>p<\/jats:italic>\u202f&lt;\u20090.0001; \u03c1\u00a0lower leg: <jats:italic>p<\/jats:italic>\u202f=\u20090.0098). 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\u00a0slight proximal-to-distal gradient was observed for T2<jats:sub>app<\/jats:sub> and T2-signal, but not for\u00a0\u03c1.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>PNS involvement in RRMS is characterized by a\u00a0decrease in T2<jats:sub>app<\/jats:sub> and an increase in\u00a0\u03c1, 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\u00a0better understanding of the pathophysiologic relevance of PNS involvement.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00062-022-01219-1","type":"journal-article","created":{"date-parts":[[2022,10,20]],"date-time":"2022-10-20T14:04:07Z","timestamp":1666274647000},"page":"383-392","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Quantification and Proximal-to-Distal Distribution Pattern of Tibial Nerve Lesions in Relapsing-Remitting Multiple Sclerosis"],"prefix":"10.1007","volume":"33","author":[{"given":"Adriana M.","family":"Pietsch","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Vieh\u00f6ver","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricarda","family":"Diem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Weiler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirjam","family":"Korporal-Kuhnke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brigitte","family":"Wildemann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georges","family":"Sam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M.","family":"Hayes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia","family":"F\u00f6sleitner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johann M. 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R.\u00a0Diem received grants from the German Research Foundation (FOR 2289), the Hertie Foundation, and the German Ministry of Education and Research. M.\u00a0Korporal-Kuhnke reports lecture honoraria from Novartis, BMS and Merck. O.\u00a0F\u00f6sleitner received the Rahel Goetein-Straus stipend grant from the Medical Faculty of the University of Heidelberg. J.M.E.\u00a0Jende received grants from the German Research Foundation (SFB 1158), and the International Foundation for Research in Paraplegia. S.\u00a0Heiland received a\u00a0research grant from the German Research Foundation (SFB 1118). B.\u00a0Wildemann received grants from the German Ministry of Education and Research, German Research Foundation, Dietmar Hopp Foundation and Klaus Tschira Foundation, grants and personal fees from Merck, Sanofi Genzyme, Novartis, and personal fees from Alexion, Bayer, Biogen, Teva; none related to this work. M.\u00a0Bendszus reports personal fees from Boehringer Ingelheim, grants and personal fees from Novartis, grants from Siemens, personal fees from Merck, personal fees from Bayer, grants and personal fees from Guerbet, grants from Hopp Foundation, grants from DFG, grants from European Union, grants from Stryker, personal fees from Teva, personal fees from BBraun, personal fees from Vascular Dynamics, personal fees from Grifols, personal fees from Neuroscios. J.C.\u00a0Hayes received a\u00a0research grant, personal fees, lecture honoraria and financial support for conference attendance from Alnylam Pharmaceuticals, the Olympia Morata stipend grant from the Medical Faculty of the University of Heidelberg, lecture honoraria and financial support for conference attendance from Pfizer, and advised for Akcea Therapeutics. A.M.\u00a0Pietsch, M.\u00a0Weiler, G.\u00a0Sam and J.M.\u00a0Hayes declare that they have no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}