From the Department of Neuroradiology (J.K., S.H., M.P., M.B.), Amyloidosis Center Heidelberg (J.K., U.H., J.C.P., C.K., S.O.S., E.H., A.V.K., M.W.), Department of Neuropathology (F.S.), Medical Department V (U.H., C.K., S.O.S.), Department of Neurology (J.C.P., E.H., M.W.), Division of Experimental Radiology (S.H.), Department of Neuroradiology, and Medical Department III (A.V.K.), Heidelberg University Hospital; CCU Neuropathology (F.S.), German Consortium for Translational Cancer Research, German Cancer Research Center, Heidelberg, Germany; Department of Neurology (J.M.H.), University of Michigan, Ann Arbor; Department of Pathology (C.R.), University of Kiel; and Department of Neuroradiology (M.P.), Würzburg University Hospital, Germany.
Neurology. 2017 Aug 1;89(5):475-484. doi: 10.1212/WNL.0000000000004178. Epub 2017 Jul 5.
To detect and quantify lesions of the small-caliber sural nerve (SN) in symptomatic and asymptomatic transthyretin familial amyloid polyneuropathy (TTR-FAP) by high-resolution magnetic resonance neurography (MRN) in correlation with electrophysiologic and histopathologic findings.
Twenty-five patients with TTR-FAP, 10 asymptomatic carriers of the mutated transthyretin gene (mut), and 35 age- and sex-matched healthy controls were prospectively included in this cross-sectional case-control study. All participants underwent 3T MRN with high-structural resolution (fat-saturated, T2-weighted, and double-echo sequences). Total imaging time was ≈45 minutes per patient. Manual SN segmentation was performed from its origin at the sciatic nerve bifurcation to the lower leg with subsequent evaluation of quantitative microstructural and morphometric parameters. Additional time needed for postprocessing was ≈1.5 hours per participant. Detailed neurologic and electrophysiologic examinations were conducted in the TTR group.
T2 signal and proton spin density (ρ) reliably differentiated between TTR-FAP (198.0 ± 13.3, 429.6 ± 15.25), mut carriers (137.0 ± 16.9, = 0.0009; 354.7 ± 21.64, = 0.0029), and healthy controls (90.0 ± 3.4, 258.2 ± 9.10; < 0.0001). Marked differences between mut carriers and controls were found for T2 signal ( = 0.0065) and ρ ( < 0.0001). T2 relaxation time was higher in patients with TTR-FAP only ( = 0.015 vs mut carriers, = 0.0432 vs controls). SN caliber was higher in patients with TTR-FAP vs controls and in mut carriers vs controls ( < 0.0001). Amyloid deposits were histopathologically detectable in 10 of 14 SN specimens.
SN injury in TTR-FAP is detectable and quantifiable in vivo by MRN even in asymptomatic mut carriers. Differences in SN T2 signal between controls and asymptomatic mut carriers are derived mainly from an increase of ρ, which overcomes typical limitations of established diagnostic methods as a highly sensitive imaging biomarker for early detection of peripheral nerve lesions.
This study provides Class III evidence that MRN accurately identifies asymptomatic mut carriers.
通过高分辨率磁共振神经成像（MRN）检测并量化症状性和无症状转甲状腺素蛋白家族性淀粉样多发性神经病（TTR-FAP）中小口径腓肠神经（SN）的病变，并结合电生理和组织病理学发现。
本前瞻性病例对照研究纳入了 25 例 TTR-FAP 患者、10 例携带突变转甲状腺素蛋白基因（mut）的无症状携带者和 35 名年龄和性别匹配的健康对照者。所有参与者均接受了 3T MRN 检查，具有高结构分辨率（脂肪饱和 T2 加权和双回波序列）。每位患者的总成像时间约为 45 分钟。手动对 SN 进行分段，从坐骨神经分叉处到小腿，然后评估定量微观结构和形态参数。每位参与者的后处理时间约为 1.5 小时。TTR 组进行了详细的神经和电生理检查。
T2 信号和质子自旋密度（ρ）可靠地区分了 TTR-FAP（198.0 ± 13.3，429.6 ± 15.25）、mut 携带者（137.0 ± 16.9， = 0.0009；354.7 ± 21.64， = 0.0029）和健康对照组（90.0 ± 3.4，258.2 ± 9.10； < 0.0001）。mut 携带者和对照组之间的 T2 信号（ = 0.0065）和 ρ（ < 0.0001）差异显著。仅在 TTR-FAP 患者中 T2 弛豫时间较高（ = 0.015 与 mut 携带者， = 0.0432 与对照组）。与对照组和 mut 携带者相比，TTR-FAP 患者的 SN 口径更高（ < 0.0001）。14 个 SN 标本中有 10 个可通过组织病理学检测到淀粉样沉积物。
即使在无症状 mut 携带者中，TTR-FAP 也可通过 MRN 进行体内检测和定量 SN 损伤。对照组和无症状 mut 携带者之间的 SN T2 信号差异主要源于 ρ 的增加，这克服了传统诊断方法的局限性，成为检测周围神经病变的高度敏感的影像学生物标志物。
本研究提供了 III 级证据，表明 MRN 能准确识别无症状 mut 携带者。
