Cruz Eva Sole, Fortanier Etienne, Michel Constance P, Delmont Emilien, Verschueren Annie, Hostin Marc-Adrien, Bendahan David, Attarian Shahram
Reference Center for Neuromuscular Diseases and ALS, La Timone University Hospital, Aix-Marseille University, Marseille, France.
Center for Magnetic Resonance in Biology and Medicine, Aix-Marseille University, UMR CNRS, Marseille, France.
Eur J Neurol. 2025 Apr;32(4):e70168. doi: 10.1111/ene.70168.
Hereditary transthyretin amyloid polyneuropathy (ATTRv-PN) is a rare and progressive neurodegenerative disorder characterized by axonal neuropathy and amyloid deposits. Early detection of disease onset and progression is crucial for timely therapeutic intervention. Quantitative MRI (qMRI) can be used to measure potential biomarkers. Intraepineurial fat fraction (ieFF) may reflect lipid droplets in amyloid deposits as described in histological studies or the replacement of nerve fiber loss with fatty-rich interfascicular epineurium. This study investigates the potential utility of ieFF as a novel imaging-related biomarker in differentiating ATTRv-PN, asymptomatic carriers (ATTRv-C), and healthy controls (HCs).
Fifty-three patients with TTR mutations were imaged (31 ATTRv-PN patients, 22 ATTRv-C, and 24 HC) and both clinical and electrophysiological parameters were quantified. 3D volume, ieFF, and magnetization transfer ratio (MTR) were quantified in sciatic and tibial nerves using qMRI.
Symptomatic ATTRv-PN patients exhibited significantly higher ieFF in both sciatic (32.4% IQR [24.4-38.1]) and tibial nerves (13.7%, IQR [9.97-20.7]) compared to controls (sciatic 22.3%, IQR [16.6-28.5]; tibial 9.74%, IQR [6.36-12.5]) (p < 0.05). ieFF values were positively correlated in both uni and multivariate analyses with the main clinical scores and electrophysiological measures. ATTRv-C also showed increased ieFF values compared to controls (p < 0.05). Comparatively, MTR and nerve volumes exhibited less pronounced differences across groups.
This study demonstrates that ieFF effectively differentiates symptomatic and asymptomatic ATTRv patients from HC and correlates strongly with electrophysiological and clinical severity parameters. Furthermore, we compare ieFF with conventional qMRI biomarkers, highlighting its superior potential for monitoring nerve structural impairment.
遗传性转甲状腺素蛋白淀粉样多神经病（ATTRv-PN）是一种罕见的进行性神经退行性疾病，其特征为轴索性神经病和淀粉样沉积物。疾病发作和进展的早期检测对于及时的治疗干预至关重要。定量MRI（qMRI）可用于测量潜在的生物标志物。神经内膜脂肪分数（ieFF）可能反映淀粉样沉积物中的脂滴，如组织学研究中所述，或富含脂肪的束间神经内膜替代神经纤维损失的情况。本研究调查了ieFF作为一种新型成像相关生物标志物在鉴别ATTRv-PN、无症状携带者（ATTRv-C）和健康对照（HC）中的潜在效用。
对53例携带TTR突变的患者进行成像（31例ATTRv-PN患者、22例ATTRv-C和24例HC），并对临床和电生理参数进行量化。使用qMRI对坐骨神经和胫神经的三维体积、ieFF和磁化传递率（MTR）进行量化。
有症状的ATTRv-PN患者坐骨神经（32.4%，四分位数间距[IQR][24.4-38.1]）和胫神经（13.7%，IQR[9.97-20.7]）的ieFF均显著高于对照组（坐骨神经22.3%，IQR[16.6-28.5]；胫神经9.74%，IQR[6.36-12.5]）（p<0.05）。在单变量和多变量分析中，ieFF值与主要临床评分和电生理指标均呈正相关。与对照组相比，ATTRv-C的ieFF值也有所升高（p<0.05）。相比之下，MTR和神经体积在各组间的差异不太明显。
本研究表明，ieFF能有效区分有症状和无症状的ATTRv患者与HC，并与电生理和临床严重程度参数密切相关。此外，我们将ieFF与传统的qMRI生物标志物进行了比较，突出了其在监测神经结构损伤方面的优越潜力。
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