PDF(Pubmed)
Abstract：
Amyotrophic lateral sclerosis 8 (ALS8) is a predominantly lower motor neuron syndrome originally described in a Portuguese-Brazilian family, which originated from a common founder. ALS8 is caused by a VAPB mutation and extremely rare in Central Europe. We present a 51-year-old German man with ALS8 who had the P56S VAPB mutation independently of the founder effect. In the final 4 years of his life (disease duration 10 years), the patient had five MRI scans and four in-depth neuropsychological assessments. This paper addresses the course of the patient\'s cognitive status and relates cognitive performance to structural brain changes in order to determine whether this ALS8 case showed a different pattern of cognitive decline compared with sporadic ALS. The executive functions, verbal fluency, and memory of the patient and 17 age-, sex-, and education-matched controls were assessed on four different occasions. His cognitive performance and decline were investigated for abnormality using cross-sectional and longitudinal matched case-control analysis. We obtained five T1-weighted MRI, which we analyzed using voxel-wise non-parametric analysis with statistical non-parametric mapping in Matlab. Moreover, we conducted a single-subject correlation between cognitive performance and brain atrophy. The cognitive profile of the index patient featured executive dysfunction. Notably, his working memory and shifting ability declined from a healthy baseline to an impaired performance, leading to a transition from cognitively non-impaired (ALSni) to cognitively impaired (ALSci). The correlations we observed between cerebellar atrophy and verbal fluency in addition to fusiform gyrus atrophy and shifting are novel findings. We found that the conversion from ALSni to ALSci was associated with widespread cerebral atrophy, which extended beyond the primary motor and premotor cortex and affected, among others, the cerebellum and left fusiform gyrus. The index patients\' cognitive profile resembles that of other ALS phenotypes, but the extensive atrophy beyond extra-motor areas has not yet been described.
摘要：
肌萎缩侧索硬化症8（ALS8）是一种主要的下运动神经元综合征，最初在葡萄牙-巴西家庭中描述。它起源于一个共同的创始人。ALS8是由VAPB突变引起的，在中欧极为罕见。我们介绍了一名患有ALS8的51岁德国男子，他的P56SVAPB突变与创始人效应无关。在他生命的最后4年（疾病持续时间10年），患者接受了5次MRI扫描和4次深入神经心理学评估.本文讨论了患者认知状态的过程，并将认知表现与大脑结构变化联系起来，以确定与散发性ALS相比，该ALS8病例是否表现出不同的认知下降模式。执行功能，口语流利,对病人和17岁的记忆，sex-,和教育匹配的对照在四个不同的场合进行评估.使用横截面和纵向匹配的病例对照分析研究了他的认知表现和下降的异常。我们获得了五个T1加权MRI，我们在Matlab中使用基于体素的非参数分析和统计非参数映射进行分析。此外，我们对认知表现和脑萎缩进行了单受试者相关性研究.指标患者的认知特征为执行功能障碍。值得注意的是,他的工作记忆和转移能力从健康的基线下降到表现受损，导致从认知非受损（ALSni）过渡到认知受损（ALSci）。除了梭状回萎缩和移位外，我们还观察到小脑萎缩和言语流畅性之间的相关性是新发现。我们发现从ALSni到ALSci的转化与广泛的脑萎缩有关，延伸到初级运动和运动前皮层之外，其中,小脑和左梭状回。指数患者的认知特征与其他ALS表型相似，但是运动外区域以外的广泛萎缩尚未被描述。
