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While peripheral nerve involvement is frequent in spastic paraplegia 7 (SPG7), the evidence of peripheral nerve involvement in SPG4 is more controversial. We aimed to characterize lower extremity peripheral nerve involvement in SPG4 and SPG7 by quantitative magnetic resonance neurography (MRN).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Twenty\u2010six HSP patients carrying either the SPG4 or SPG7 mutation and 26 age\u2010\/sex\u2010matched healthy controls prospectively underwent high\u2010resolution MRN with large coverage of the sciatic and tibial nerve. Dual\u2010echo turbo\u2010spin\u2010echo sequences with spectral fat\u2010saturation were utilized for T2\u2010relaxometry and morphometric quantification, while two gradient\u2010echo sequences with and without an off\u2010resonance saturation rapid frequency pulse were applied for magnetization transfer contrast (MTC) imaging. HSP patients additionally underwent detailed neurologic and electroneurographic assessments.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>All microstructural (proton spin density [\u03c1], T2\u2010relaxation time, magnetization transfer ratio) and morphometric (cross\u2010sectional area) quantitative MRN markers were decreased in SPG4 and SPG7 indicating chronic axonopathy. \u03c1 was superior in differentiating subgroups and identifying subclinical nerve damage in SPG4 and SPG7 without neurophysiologic signs of polyneuropathy. MRN markers correlated well with clinical scores and electroneurographic results.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>MRN characterizes peripheral nerve involvement in SPG4 and SPG7 as a neuropathy with predominant axonal loss. Evidence of peripheral nerve involvement in SPG4 and SPG7, even without electroneurographically manifest polyneuropathy, and the good correlation of MRN markers with clinical measures of disease progression, challenge the traditional view of the existence of HSPs with isolated pyramidal signs and suggest MRN markers as potential progression biomarkers in HSP.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ene.15841","type":"journal-article","created":{"date-parts":[[2023,5,8]],"date-time":"2023-05-08T11:33:57Z","timestamp":1683545637000},"page":"2442-2452","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Peripheral nerve involvement in hereditary spastic paraplegia characterized by quantitative magnetic resonance 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