The University of Sydney, Sydney, New South Wales, Australia.
Sydney Children's Hospitals Network (Randwick and Westmead), Sydney, New South Wales, Australia.
Brain. 2018 Dec 1;141(12):3319-3330. doi: 10.1093/brain/awy280.
Many genetic subtypes of Charcot-Marie-Tooth disease (CMT) show signs of symptomatic disease during the earliest years of life. This might be the ideal time to intervene before progression of clinical sequelae due to demyelination and axonal loss. In the absence of disease-specific clinical trial outcome measures for CMT during infancy and early childhood the aim of this study was to develop and validate a functional measure of disease severity, known as the Charcot-Marie-Tooth disease Infant Scale (CMTInfS). Development projects involved identification of a preliminary pool of 31 items representing the range of disability in affected patients aged 0-4 years from a systematic review of the literature, peer review by 12 expert clinicians and researchers in the field, design of a scoring algorithm and pilot testing in 22 participants. Subsequently, a series of validation projects were conducted based on 128 assessments of: 26 confirmed cases of inherited neuropathy (17 CMT1A, one CMT1B, one CMT1D, one CMT2C, one CMT2S, two CMT4C, one CMTX3, one Riboflavin Transporter Deficiency Type 2, and one unidentified mutation); seven 'at risk' cases and 95 unaffected healthy controls recruited through the NIH-funded Inherited Neuropathies Consortium. Validation projects included: Item, Factor and Rasch analysis, intra- and inter-rater reliability, discriminant ability and convergent validity with the CMT Pediatric Scale (CMTPedS) for children aged 3-4 years. Development and validation projects produced a psychometrically robust 15-item scale. Rasch analysis supported the viability of the CMTInfS as a unidimensional measure of disease severity and showed good overall model fit, no evidence of misfitting items or persons and was well targeted for affected children. The CMTInfS demonstrated high intra-rater reliability [intraclass correlation coefficient (ICC)3,1 0.999, 95% confidence interval 0.996-1.000) and inter-rater reliability (ICC2,1 0.997, 95% confidence interval 0.992-0.999). The CMTInfS was able to discriminate between the CMT group and controls (P = 0.006), and convergent validity demonstrated good agreement between CMTInfS and CMTPedS scores (r = 0.76, P = 0.01). The final version of the CMTInfS requires 20 min to administer and is a reliable and sensitive functional outcome measure for early onset CMT and related neuropathies.10.1093/brain/awy280_video1awy280media15970672819001.
许多遗传性神经病（CMT）亚型在生命的最早几年就出现了有症状的疾病迹象。这可能是在脱髓鞘和轴突丢失导致临床后遗症进展之前进行干预的理想时机。在婴儿期和幼儿期缺乏针对 CMT 的特定临床试验结局指标的情况下，本研究旨在开发和验证一种疾病严重程度的功能测量方法，称为 Ch arcot-Marie-Tooth 疾病婴儿量表（CMTInfS）。开发项目涉及从文献系统回顾中确定一个初步的 31 项项目库，代表受影响的 0-4 岁患者的残疾范围，该项目库由 12 名神经病学专家临床医生和研究人员进行同行评审，设计评分算法，并在 22 名参与者中进行试点测试。随后，根据 128 项评估进行了一系列验证项目：26 例遗传性神经病确诊病例（17 例 CMT1A，1 例 CMT1B，1 例 CMT1D，1 例 CMT2C，1 例 CMT2S，2 例 CMT4C，1 例 CMTX3，1 例核黄素转运蛋白缺乏 2 型和 1 例未识别突变）；7 例“高危”病例和 95 名无症状健康对照者通过 NIH 资助的遗传性神经病学联合会招募。验证项目包括：项目、因素和 Rasch 分析、内部和外部评分者可靠性、判别能力以及与 3-4 岁儿童的 CMT 儿科量表（CMTPedS）的收敛效度。开发和验证项目产生了一个具有良好心理测量学可靠性的 15 项量表。Rasch 分析支持 CMTInfS 作为疾病严重程度的单一维度测量方法的可行性，并显示出良好的整体模型拟合度，没有项目或人员拟合不良的证据，并且针对受影响的儿童进行了良好的靶向定位。CMTInfS 显示出较高的内部评分者可靠性[组内相关系数（ICC）3,1 0.999，95%置信区间 0.996-1.000]和外部评分者可靠性（ICC2,1 0.997，95%置信区间 0.992-0.999）。CMTInfS 能够区分 CMT 组和对照组（P = 0.006），并且收敛效度表明 CMTInfS 与 CMTPedS 评分之间具有良好的一致性（r = 0.76，P = 0.01）。CMTInfS 的最终版本需要 20 分钟来完成，是一种用于早期 CMT 和相关神经病的可靠且敏感的功能结局测量方法。
