Department of Neurology, Heidelberg University Hospital, Heidelberg, Germany.
Department of Neuroradiology, Heidelberg University Hospital, Heidelberg, Germany.
Eur J Neurol. 2023 Aug;30(8):2442-2452. doi: 10.1111/ene.15841. Epub 2023 May 26.
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).
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.
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.
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.
遗传性痉挛性截瘫（HSPs）是一种异质性遗传疾病。虽然在痉挛性截瘫 7 型（SPG7）中经常涉及周围神经受累，但 SPG4 中存在周围神经受累的证据更具争议性。我们旨在通过定量磁共振神经成像（MRN）来描述 SPG4 和 SPG7 下肢周围神经受累情况。
26 名携带 SPG4 或 SPG7 突变的 HSP 患者和 26 名年龄/性别匹配的健康对照者前瞻性接受了坐骨神经和胫神经大覆盖范围的高分辨率 MRN。采用双回波涡轮自旋回波序列结合频谱脂肪饱和进行 T2 弛豫时间和形态计量学定量，而采用两个梯度回波序列，分别带有和不带有离共振饱和快速频率脉冲进行磁共振转移对比（MTC）成像。HSP 患者还接受了详细的神经学和电神经图评估。
所有微观结构（质子自旋密度[ρ]、T2 弛豫时间、磁共振转移率）和形态计量学（横截面积）定量 MRN 标志物在 SPG4 和 SPG7 中均降低，表明存在慢性轴突病变。ρ 在区分亚组和识别 SPG4 和 SPG7 中的亚临床神经损伤方面更具优势，而没有神经电生理学多发性神经病迹象。MRN 标志物与临床评分和电神经图结果相关性良好。
MRN 特征性地描述了 SPG4 和 SPG7 中的周围神经受累为神经病，以轴突丢失为主。即使没有电神经图表现出的多发性神经病，在 SPG4 和 SPG7 中也存在周围神经受累的证据，以及 MRN 标志物与疾病进展的临床测量之间的良好相关性，挑战了 HSP 中存在单纯锥体征的传统观点，并提示 MRN 标志物作为 HSP 中的潜在进展生物标志物。
