Division of Neuroimaging Research, Barrow Neurological Institute, Phoenix, Arizona, USA.
Department of Neurology, Vanderbilt University, Nashville, Tennessee, USA.
Ann Clin Transl Neurol. 2022 Jul;9(7):925-935. doi: 10.1002/acn3.51561. Epub 2022 Jun 3.
Charcot-Marie-Tooth type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsy (HNPP) are caused by mutations to the peripheral myelin protein 22 (PMP22) gene. A need exists for sensitive and reliable biomarkers of progression and treatment response. Magnetic resonance imaging (MRI) metrics of nerve pathology and morphology were investigated for this purpose.
MRI was performed at 3.0 T in the thigh of CMT1A (N = 11) and HNPP patients (N = 12) and controls (N = 23). Three potential imaging biomarkers of the sciatic nerve were investigated: 1) magnetization transfer ratio (MTR), which assays myelin content, and 2) cross-sectional area (CSA) and 3) circularity, which assay morphological changes. Potential imaging biomarkers were compared across cohorts and assessed for relationships with disability in the legs (CMTES ), compound motor action potentials (CMAP), and motor conduction velocities (MCV). Inter-rater reliability and test-retest repeatability were established for each imaging metric.
Significant differences in MTR, CSA, and circularity were observed in CMT1A relative to controls (p = 0.02, p < 0.001, and p = 0.003, respectively, via Wilcoxon rank-sum tests). Differences were not observed in the HNPP cohort. Significant relationships were observed between MTR and clinical metrics (CMTES : p = 0.003, CMAP: p = 0.03, MCV: p = 0.01); and between CSA and electrophysiology (CMAP: p = 0.002, MCV: p < 0.001). All metrics were reliable and repeatable with MTR the most reliable (intraclass correlation coefficient [ICC] >0.999, CV = 0.30%) and repeatable (ICC = 0.84, CV = 3.16%).
MTR, CSA, and circularity showed promise as reliable and sensitive biomarkers of CMT1A, but not HNPP. These warrant longitudinal investigation as response biomarkers in upcoming clinical trials of CMT1A, while other methods should be considered for HNPP.
Charcot-Marie-Tooth 型 1A（CMT1A）和遗传性压力易感性神经病（HNPP）是由周围髓鞘蛋白 22（PMP22）基因突变引起的。目前需要寻找敏感且可靠的疾病进展和治疗反应生物标志物。为此，研究了磁共振成像（MRI）神经病理学和形态学指标。
在 3.0T 磁共振仪上对 CMT1A（N=11）和 HNPP 患者（N=12）以及对照组（N=23）的大腿进行 MRI 检查。研究了 3 种潜在的坐骨神经成像生物标志物：1）磁化传递率（MTR），用于评估髓鞘含量，2）横截面积（CSA）和 3）圆形度，用于评估形态变化。比较了不同队列中的潜在成像生物标志物，并评估了其与腿部 CMTES（复合运动动作电位）、CMAP（运动传导速度）和 MCV（运动传导速度）之间的关系。对每个成像指标的组内相关系数（ICC）和测试-重测重复性进行了评估。
与对照组相比，CMT1A 患者的 MTR、CSA 和圆形度存在显著差异（通过 Wilcoxon 秩和检验，p=0.02、p<0.001 和 p=0.003）。HNPP 队列中未观察到差异。MTR 与临床指标（CMTES：p=0.003，CMAP：p=0.03，MCV：p=0.01）和 CSA 与电生理学（CMAP：p=0.002，MCV：p<0.001）之间存在显著相关性。所有指标均具有可靠性和可重复性，其中 MTR 的可靠性最高（组内相关系数[ICC]＞0.999，变异系数[CV]＝0.30%）和重复性最好（ICC＝0.84，CV＝3.16%）。
MTR、CSA 和圆形度有望成为 CMT1A 的可靠且敏感的生物标志物，但不适用于 HNPP。这些生物标志物需要进行纵向研究，作为 CMT1A 即将进行的临床试验中的治疗反应生物标志物，而对于 HNPP 则需要考虑其他方法。
