BACKGROUND:After the demonstration of a corticoefferent propagation pattern in amyotrophic lateral sclerosis (ALS) by neuropathological studies, this concept has been used for in vivo staging of individual patients by diffusion tensor imaging (DTI) techniques, both in `classical` ALS and in restricted phenotypes such as primary lateral sclerosis (PLS). OBJECTIVE:The study was designed to investigate that microstructural changes according to the neuropathologically defined ALS alteration pattern in PLS patients could be confirmed to be identical to ´classical´ ALS patients. The novelty in this approach is that the results were independent of the subject samples and the data acquisition parameters (as was validated in two samples from two different centres). That way, reproducibility across (international) centres in addition to harmonisation/standardisation of data analysis has been addressed, for the possible use of MRI-based staging to stratify patients in clinical trials. METHODS:Tractwise analysis of fractional anisotropy (FA) maps according to the ALS-staging pattern was applied to DTI data (pooled from two ALS centres) of 88 PLS patients and 88 ALS patients with a 'classical' phenotype in comparison to 88 matched controls in order to identify white matter integrity alterations. RESULTS:In the tract-specific analysis, alterations were identical for PLS and ALS in the tract systems corresponding to the ALS staging pattern, independent of the subject samples and the data acquisition parameters. The individual categorisation into ALS stages did not differ between PLS and ALS patients. CONCLUSIONS:This DTI study in a two-centre setting demonstrated that the neuropathological stages can be mapped in vivo in PLS with high reproducibility and that PLS-associated cerebral propagation, although showing the same corticofugal patterns as ALS, might have a different time course of neuropathology, in analogy to its much slower clinical progression rates.

译文

背景:在通过神经病理学研究证实了肌萎缩性侧索硬化症(ALS)的皮质介导的传播方式之后,该概念已通过扩散张量成像(DTI)技术用于个别患者的体内分期,无论是在“经典” ALS中还是在限制性表型,例如原发性侧索硬化症(PLS)。
目的:本研究旨在调查根据神经病理学定义的ALS改变模式在PLS患者中的微结构变化可被证实与“经典” ALS患者相同。这种方法的新颖之处在于结果独立于主题样本和数据采集参数(已在来自两个不同中心的两个样本中进行了验证)。这样,除了可以统一/标准化的数据分析外,还解决了跨(国际)中心的可重复性问题,从而可以在临床试验中使用基于MRI的分期对患者进行分层。
方法:将根据ALS分期模式进行的分数各向异性(FA)图的逐行分析应用于88个PLS患者和88个具有'经典'表型的ALS患者的DTI数据(从两个ALS中心汇集),而与88个匹配对照组进行比较为了识别白质完整性改变。
结果:在特定于管道的分析中,对应于ALS分期模式的管道系统中PLS和ALS的变化是相同的,独立于受试者样本和数据采集参数。在PLS和ALS患者之间,进入ALS阶段的个体分类没有差异。
结论:这项在两个中心的DTI研究表明,神经病理学阶段可以在PLS中以高再现性进行体内定位,并且与PLS相关的脑部繁殖,尽管显示出与ALS相同的皮质型,但可能具有不同的时程。神经病理学,类似于它的临床进展速度要慢得多。

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