Department of Neurology, University of Colorado Denver, Aurora, CO, USA.
Department of Child Neurology, Scientific Institute for Research and Health Care Foundation Carlo Besta Neurological Institute, Milan, Italy.
Ann Neurol. 2023 Mar;93(3):563-576. doi: 10.1002/ana.26518. Epub 2022 Oct 28.
The paucity of longitudinal natural history studies in MPZ neuropathy remains a barrier to clinical trials. We have completed a longitudinal natural history study in patients with MPZ neuropathies across 13 sites of the Inherited Neuropathies Consortium.
Change in Charcot-Marie-Tooth Examination Score (CMTES) and Rasch modified CMTES (CMTES-R) were evaluated using longitudinal regression over a 5-year period in subjects with MPZ neuropathy. Data from 139 patients with MPZ neuropathy were examined.
The average baseline CMTES and CMTES-R were 10.84 (standard deviation [SD] = 6.0, range = 0-28) and 14.60 (SD = 7.56, range = 0-32), respectively. A mixed regression model showed significant change in CMTES at years 2-5 (mean change from baseline of 0.87 points at 2 years, p = 0.008). Subgroup analysis revealed greater change in CMTES at 2 years in subjects with axonal as compared to demyelinating neuropathy (mean change of 1.30 points [p = 0.016] vs 0.06 points [p = 0.889]). Patients with a moderate baseline neuropathy severity also showed more notable change, by estimate, than those with mild or severe neuropathy (mean 2-year change of 1.14 for baseline CMTES 8-14 [p = 0.025] vs -0.03 for baseline CMTES 0-7 [p = 0.958] and 0.25 for baseline CMTES ≥ 15 [p = 0.6897]). The progression in patients harboring specific MPZ mutations was highly variable.
CMTES is sensitive to change over time in adult patients with axonal but not demyelinating forms of MPZ neuropathy. Change in CMTES was greatest in patients with moderate baseline disease severity. These findings will inform future clinical trials of MPZ neuropathies. ANN NEUROL 2023;93:563-576.
MPZ 神经病的纵向自然病史研究甚少，这仍是临床试验的障碍。我们已在遗传性神经病学联合会的 13 个研究点完成了一项 MPZ 神经病患者的纵向自然病史研究。
对患有 MPZ 神经病的受试者，在 5 年期间使用纵向回归分析变化，观察 Charcot-Marie-Tooth 检查评分（CMTES）和改良 Rasch CMTES（CMTES-R）的变化。共分析了 139 例 MPZ 神经病患者的数据。
平均基线 CMTES 和 CMTES-R 分别为 10.84（标准差 [SD] 6.0，范围 0-28）和 14.60（SD 7.56，范围 0-32）。混合回归模型显示，2-5 年 CMTES 有显著变化（从基线的平均变化为 2 年时 0.87 分，p=0.008）。亚组分析显示，轴索性神经病与脱髓鞘性神经病相比，2 年时 CMTES 变化更大（平均变化 1.30 分 [p=0.016] vs 0.06 分 [p=0.889]）。基线神经病严重程度为中度的患者变化更为明显，估计值高于轻度或重度神经病患者（CMTES 基线 8-14 的 2 年平均变化为 1.14 [p=0.025]，CMTES 基线 0-7 的为 -0.03 [p=0.958]，CMTES 基线≥15 的为 0.25 [p=0.6897]）。携带特定 MPZ 突变的患者进展差异很大。
CMTES 对轴索性但不是脱髓鞘性 MPZ 神经病成年患者的时间变化敏感。CMTES 的变化在基线疾病严重程度中度的患者中最大。这些发现将为未来的 MPZ 神经病临床试验提供信息。
