Peripheral Nerve Involvement in Friedreich's Ataxia Characterized by Quantitative Magnetic Resonance Neurography

IF 4.5 2区医学 Q1 CLINICAL NEUROLOGY

European Journal of Neurology Pub Date : 2025-03-25 DOI:10.1111/ene.70121

Heike Jacobi, Markus Weiler, Georges Sam, Sabine Heiland, John M. Hayes, Martin Bendszus, Wolfgang Wick, Jennifer C. Hayes

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Abstract

Background

Friedreich's ataxia (FRDA) affects both the central and peripheral nervous system. Peripheral nerve involvement manifests predominantly as a progressive sensory neuropathy caused by dorsal root ganglionopathy. An additional direct involvement of peripheral nerves leading to abnormal myelination is increasingly discussed. Here, we characterize lower extremity peripheral nerve involvement in FRDA by quantitative magnetic resonance neurography (MRN).

Methods

Sixteen genetically confirmed FRDA patients and 16 age-/sex-matched controls were prospectively enrolled. Patients underwent neurologic examinations and nerve conduction studies (NCS). Large-coverage MRN of sciatic and tibial nerves was conducted utilizing dual-echo turbo-spin-echo sequences with spectral fat saturation for T2-relaxometry, and two gradient-echo sequences with and without off-resonance saturation rapid frequency pulses for magnetization transfer contrast imaging. Microstructural and morphometric MRN markers including T2-relaxation time (T2_app), proton spin density (ρ), magnetization transfer ratio (MTR), and cross-sectional area (CSA) were calculated to characterize nerve lesions.

Results

Tibial nerve ρ and T2_app were markedly decreased in FRDA at the thigh (ρ: 368.4 ± 11.0 a.u.; T2_app: 59.5 ± 1.8 ms) and lower leg (ρ: 337.3 ± 12.6 a.u.; T2_app: 53.9 ± 1.4 ms) versus controls (thigh, ρ: 458.9 ± 9.5 a.u., p < 0.0001; T2_app: 66.3 ± 0.8 ms, p = 0.0019; lower leg, ρ: 449.9 ± 12.1 a.u., p < 0.0001; T2_app: 62.4 ± 1.2 ms, p < 0.0001) and correlated well with clinical scores, disease duration, and NCS. MTR and CSA did not differentiate between FRDA and controls.

Conclusion

Our study results provide a profound characterization of peripheral nerve involvement in FRDA. The identified good correlation between ρ and T2_app with clinical symptom scores and NCS suggests that parameters of T2 relaxometry may become relevant biomarkers to monitor disease progression and therapeutic responses in potential future clinical trials.

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定量磁共振神经造影表征弗里德赖希共济失调的周围神经受累

弗里德赖希共济失调（FRDA）影响中枢和周围神经系统。周围神经受累主要表现为由背根神经节病引起的进行性感觉神经病变。另一种直接累及外周神经导致髓鞘形成异常的疾病被越来越多地讨论。在这里，我们通过定量磁共振神经成像（MRN）表征FRDA的下肢周围神经受累。方法前瞻性纳入16例基因证实的FRDA患者和16例年龄/性别匹配的对照组。患者接受神经学检查和神经传导研究（NCS）。采用脂肪饱和谱双回波涡轮自旋回波序列对坐骨神经和胫骨神经进行大覆盖磁共振成像（MRN），带和不带非共振饱和快速频率脉冲的梯度回波序列进行磁化转移对比成像（mri）。计算微观结构和形态测量的MRN标记，包括t2松弛时间（T2app）、质子自旋密度（ρ）、磁化传递比（MTR）和横截面积（CSA）来表征神经病变。结果股骨FRDA后胫骨神经ρ和T2app明显降低(ρ: 368.4±11.0 a.u；T2app: 59.5±1.8 ms)和小腿(ρ:337.3±12.6 a.u。;T2app: 53.9±1.4 ms)和控制(大腿,ρ:458.9±9.5 a.u。， p < 0.0001；T2app: 66.3±0.8 ms, p = 0.0019；小腿ρ: 449.9±12.1 a.u.， p < 0.0001；T2app: 62.4±1.2 ms, p < 0.0001)，与临床评分、病程、NCS有良好的相关性。MTR和CSA没有区分FRDA和对照。结论我们的研究结果提供了FRDA周围神经受累的深刻特征。ρ和T2app与临床症状评分和NCS之间的良好相关性表明，T2松弛测量参数可能成为未来临床试验中监测疾病进展和治疗反应的相关生物标志物。

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来源期刊

European Journal of Neurology 医学-临床神经学

CiteScore

9.70

自引率

2.00%

发文量

418

审稿时长

1 months

期刊介绍： The European Journal of Neurology is the official journal of the European Academy of Neurology and covers all areas of clinical and basic research in neurology, including pre-clinical research of immediate translational value for new potential treatments. Emphasis is placed on major diseases of large clinical and socio-economic importance (dementia, stroke, epilepsy, headache, multiple sclerosis, movement disorders, and infectious diseases).