Peripheral nerve involvement in both SPG4 and SPG7
Magnetic resonance neurography (MRN) markers of sciatic and tibial nerves correlate well with clinical markers of disease progression in both SPG4 and SPG7, where previously evidence of peripheral nerve involvement in SPG4 has been controversial.
These results challenge the traditional view of HSPs with isolated pyramidal signs and suggest MRN markers as potential biomarkers of HSP progression.
Background and objectives: Hereditary spastic paraplegias (HSPs) are heterogenous genetic disorders. 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).
Methods: Twenty-six HSP patients carrying either the SPG4 or SPG7 mutation and 26 age-/sex-matched healthy controls prospectively underwent high-resolution MRN with large coverage of the sciatic and tibial nerve. Dual-echo turbo-spin-echo sequences with spectral fat-saturation were utilized for T2-relaxometry and morphometric quantification, while two gradient-echo sequences with and without an off-resonance saturation rapid frequency pulse were applied for magnetization transfer contrast (MTC) imaging. HSP patients additionally underwent detailed neurologic and electroneurographic assessments.
Results: All microstructural (proton spin density [ρ], T2-relaxation time, magnetization transfer ratio) and morphometric (cross-sectional area) quantitative MRN markers were decreased in SPG4 and SPG7 indicating chronic axonopathy. ρ 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.
Conclusions: 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.
SOURCE: Eur J Neurol. 2023 Aug;30(8):2442-2452.
doi: 10.1111/ene.15841. Epub 2023 May 26. PMID: 37154411 © 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.
Peripheral nerve involvement in hereditary spastic paraplegia characterized by quantitative magnetic resonance neurography
1. Department of Neurology, Heidelberg University Hospital, Heidelberg, Germany.
2. Department of Neuroradiology, Heidelberg University Hospital, Heidelberg, Germany.
3. Division of Experimental Radiology, Department of Neuroradiology, Heidelberg University Hospital, Heidelberg, Germany.
4. Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA.
5. Center for Neurology and Hertie Institute for Clinical Brain Research, University Hospital, Tübingen, Germany.
6. German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.