Quattrone Andrea, Franzmeier Nicolai, Huppertz Hans-Jürgen, Klietz Martin, Roemer Sebastian N, Boxer Adam L, Levin Johannes, Höglinger Günter U
Department of Neurology, University Hospital, LMU Munich, Munich, Germany.
Institute of Neurology, Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy.
Mov Disord. 2024 Aug;39(8):1329-1342. doi: 10.1002/mds.29866. Epub 2024 Jun 2.
Several magnetic resonance imaging (MRI) measures have been suggested as progression biomarkers in progressive supranuclear palsy (PSP), and some PSP staging systems have been recently proposed.
Comparing structural MRI measures and staging systems in tracking atrophy progression in PSP and estimating the sample size to use them as endpoints in clinical trials.
Progressive supranuclear palsy-Richardson's syndrome (PSP-RS) patients with one-year-follow-up longitudinal brain MRI were selected from the placebo arms of international trials (NCT03068468, NCT01110720, NCT01049399) and the DescribePSP cohort. The discovery cohort included patients from the NCT03068468 trial; the validation cohort included patients from other sources. Multisite age-matched healthy controls (HC) were included for comparison. Several MRI measures were compared: automated atlas-based volumetry (44 regions), automated planimetric measures of brainstem regions, and four previously described staging systems, applied to volumetric data.
Of 508 participants, 226 PSP patients including discovery (n = 121) and validation (n = 105) cohorts, and 251 HC were included. In PSP patients, the annualized percentage change of brainstem and midbrain volume, and a combined index including midbrain, frontal lobe, and third ventricle volume change, were the progression biomarkers with the highest effect size in both cohorts (discovery: >1.6; validation cohort: >1.3). These measures required the lowest sample sizes (n < 100) to detect 30% atrophy progression, compared with other volumetric/planimetric measures and staging systems.
This evidence may inform the selection of imaging endpoints to assess the treatment efficacy in reducing brain atrophy rate in PSP clinical trials, with automated atlas-based volumetry requiring smaller sample size than staging systems and planimetry to observe significant treatment effects. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
几种磁共振成像（MRI）测量方法已被提议作为进行性核上性麻痹（PSP）的疾病进展生物标志物，并且最近提出了一些PSP分期系统。
比较结构MRI测量方法和分期系统在追踪PSP萎缩进展情况以及估计将其用作临床试验终点的样本量方面的效果。
从国际试验（NCT03068468、NCT01110720、NCT01049399）的安慰剂组和DescribePSP队列中选取有一年随访期的纵向脑MRI的进行性核上性麻痹-理查森综合征（PSP-RS）患者。发现队列包括来自NCT03068468试验的患者；验证队列包括来自其他来源的患者。纳入多中心年龄匹配的健康对照（HC）进行比较。比较了几种MRI测量方法：基于图谱的自动体积测量法（44个区域）、脑干区域的自动平面测量法以及应用于体积数据的四种先前描述的分期系统。
在508名参与者中，纳入了226名PSP患者，包括发现队列（n = 121）和验证队列（n = 105），以及251名HC。在PSP患者中，脑干和中脑体积的年化百分比变化以及包括中脑、额叶和第三脑室体积变化的综合指数，是两个队列中效应量最高的疾病进展生物标志物（发现队列：>1.6；验证队列：>1.3）。与其他体积/平面测量方法和分期系统相比，这些测量方法检测30%萎缩进展所需的样本量最小（n < 100）。
这一证据可为选择成像终点以评估PSP临床试验中降低脑萎缩率的治疗效果提供参考，基于图谱的自动体积测量法观察到显著治疗效果所需的样本量比分期系统和平面测量法更小。© 2024作者。《运动障碍》由Wiley Periodicals LLC代表国际帕金森和运动障碍协会出版。
