背景:无已知遗传或获得性原因的散发性成人共济失调可分为多系统小脑型萎缩(MSA-C)和病因不明的散发性成人共济失调(SAOA)。
目的:研究两种条件的差异演变,包括血浆神经丝轻链(NfL)水平和磁共振成像(MRI)标记。
方法:SPORTAX是对发病>40年的散发性共济失调患者的前瞻性登记。共济失调评估和评级量表是主要结果指标。在子组中,采集血液样本并进行MRI检查.通过单分子测定测量血浆NfL。自动测量局部脑体积。要评估信号变化,我们定义了脑桥和小脑中部花梗异常评分(PMAS)。使用混合效果模型,我们分析了从共济失调开始的时间尺度上的变化.
结果:在404个没有基因诊断的患者中,130符合基线可能的MSA-C标准,26符合随访期间提示临床转换为MSA-C。其余248人被归类为SAOA。在基线,NFL,小脑白质(CWM)和脑桥体积,和PMAS从SAOA中分离MSA-C。NfL在MSA-C中降低,而在SAOA中没有改变。CWM和脑桥体积下降得更快,而在MSA-C中PMAS增加更快。在MSA-C,脑桥体积对变化的敏感性最高,PMAS是较快进展的预测因子。满足可能的MSA标准,NfL和PMAS是危险因素,转换为MSA-C的CWM和桥体积保护因子
结论:本研究提供了MSA-C和SAOA中生物标志物差异进化和预后相关性的详细信息。©2023作者。由WileyPeriodicalsLLC代表国际帕金森症和运动障碍协会出版的运动障碍。
Sporadic adult-onset ataxias without known genetic or acquired cause are subdivided into multiple system atrophy of cerebellar type (MSA-C) and sporadic adult-onset ataxia of unknown etiology (SAOA).
To study the differential evolution of both conditions including plasma neurofilament light chain (NfL) levels and magnetic resonance imaging (MRI) markers.
SPORTAX is a prospective registry of sporadic ataxia patients with an onset >40 years. Scale for the Assessment and Rating of Ataxia was the primary outcome measure. In subgroups, blood samples were taken and MRIs performed. Plasma NfL was measured via a single molecule assay. Regional brain volumes were automatically measured. To assess signal changes, we defined the pons and middle cerebellar peduncle abnormality score (PMAS). Using mixed-effects models, we analyzed changes on a time scale starting with ataxia onset.
Of 404 patients without genetic diagnosis, 130 met criteria of probable MSA-C at baseline and 26 during follow-up suggesting clinical conversion to MSA-C. The remaining 248 were classified as SAOA. At baseline, NfL, cerebellar white matter (CWM) and pons volume, and PMAS separated MSA-C from SAOA. NfL decreased in MSA-C and did not change in SAOA. CWM and pons volume decreased faster, whereas PMAS increased faster in MSA-C. In MSA-C, pons volume had highest sensitivity to change, and PMAS was a predictor of faster progression. Fulfillment of possible MSA criteria, NfL and PMAS were risk factors, CWM and pons volume protective factors for conversion to MSA-C.
This study provides detailed information on differential evolution and prognostic relevance of biomarkers in MSA-C and SAOA. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.