Jacobi Heike, Weiler Markus, Sam Georges, Heiland Sabine, Hayes John M, Bendszus Martin, Wick Wolfgang, Hayes Jennifer C
Department of Neurology, Heidelberg University Hospital, Heidelberg, Germany.
Department of Neuroradiology, Heidelberg University Hospital, Heidelberg, Germany.
Eur J Neurol. 2025 Mar;32(3):e70121. doi: 10.1111/ene.70121.
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).
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), proton spin density (ρ), magnetization transfer ratio (MTR), and cross-sectional area (CSA) were calculated to characterize nerve lesions.
Tibial nerve ρ and T2 were markedly decreased in FRDA at the thigh (ρ: 368.4 ± 11.0 a.u.; T2: 59.5 ± 1.8 ms) and lower leg (ρ: 337.3 ± 12.6 a.u.; T2: 53.9 ± 1.4 ms) versus controls (thigh, ρ: 458.9 ± 9.5 a.u., p < 0.0001; T2: 66.3 ± 0.8 ms, p = 0.0019; lower leg, ρ: 449.9 ± 12.1 a.u., p < 0.0001; T2: 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.
Our study results provide a profound characterization of peripheral nerve involvement in FRDA. The identified good correlation between ρ and T2 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.
弗里德赖希共济失调（FRDA）会影响中枢神经系统和周围神经系统。周围神经受累主要表现为由背根神经节病变引起的进行性感觉神经病变。越来越多的讨论认为周围神经还存在直接受累导致髓鞘形成异常的情况。在此，我们通过定量磁共振神经成像（MRN）对FRDA患者下肢周围神经受累情况进行特征描述。
前瞻性纳入16例基因确诊的FRDA患者和16例年龄及性别匹配的对照者。患者接受了神经学检查和神经传导研究（NCS）。利用具有频谱脂肪饱和的双回波快速自旋回波序列进行坐骨神经和胫神经的大范围MRN检查，用于T2弛豫测量，以及利用两个分别带有和不带有失谐饱和快速频率脉冲的梯度回波序列进行磁化传递对比成像。计算包括T2弛豫时间（T2）、质子自旋密度（ρ）、磁化传递率（MTR）和横截面积（CSA）在内的微观结构和形态学MRN标记物，以表征神经病变。
与对照组相比，FRDA患者大腿部（ρ：368.4±11.0任意单位；T2：59.5±1.8毫秒）和小腿部（ρ：337.3±12.6任意单位；T2：53.9±1.4毫秒）胫神经的ρ和T2明显降低（大腿部，对照组ρ：458.9±9.5任意单位，p<0.0001；T2：66.3±0.8毫秒，p=0.0019；小腿部，对照组ρ：449.9±12.1任意单位，p<0.0001；T2：62.4±1.2毫秒，p<0.0001），且与临床评分、病程和NCS相关性良好。MTR和CSA在FRDA患者与对照组之间无差异。
我们的研究结果对FRDA患者周围神经受累情况进行了深入的特征描述。所确定的ρ和T2与临床症状评分及NCS之间的良好相关性表明，在未来潜在的临床试验中，T2弛豫测量参数可能成为监测疾病进展和治疗反应的相关生物标志物。
