Hans Berger Department of Neurology, Jena University Hospital, Jena, Germany.
Hans Berger Department of Neurology, Jena University Hospital, Jena, Germany; Center for Healthy Ageing, Jena University Hospital, Jena.
Neuroimage Clin. 2021;30:102674. doi: 10.1016/j.nicl.2021.102674. Epub 2021 Apr 15.
Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease that is characterized by a high heterogeneity in patients' disease course. Patients with bulbar onset of symptoms (b-ALS) have a poorer prognosis than patients with limb onset (l-ALS). However, neuroimaging correlates of the assumed biological difference between b-ALS and l-ALS may have been obfuscated by patients' diversity in the disease course. We conducted Voxel-Based-Morphometry (VBM) and Tract-Based-Spatial-Statistics (TBSS) in a group of 76 ALS patients without clinically relevant cognitive deficits. The subgroups of 26 b-ALS and 52 l-ALS patients did not differ in terms of disease Phase or disease aggressiveness according to the D50 progression model. VBM analyses showed widespread ALS-related changes in grey and white matter, that were more pronounced for b-ALS. TBSS analyses revealed that b-ALS was predominantly characterized by frontal fractional anisotropy decreases. This demonstrates a higher degree of neurodegenerative burden for the group of b-ALS patients in comparison to l-ALS. Correspondingly, higher bulbar symptom burden was associated with right-temporal and inferior-frontal grey matter density decreases as well as fractional anisotropy decreases in inter-hemispheric and long association tracts. Contrasts between patients in Phase I and Phase II further revealed that b-ALS was characterized by an early cortical pathology and showed a spread only outside primary motor regions to frontal and temporal areas. In contrast, l-ALS showed ongoing structural integrity loss within primary motor-regions until Phase II. We therefore provide a strong rationale to treat both onset types of disease separately in ALS studies.
肌萎缩侧索硬化症（ALS）是一种进行性神经退行性疾病，其特点是患者的疾病过程存在高度异质性。有球部症状发作的患者（b-ALS）的预后比有肢体症状发作的患者（l-ALS）差。然而，b-ALS 和 l-ALS 之间假设的生物学差异的神经影像学相关性可能因患者在疾病过程中的多样性而变得模糊。我们对 76 名无临床相关认知缺陷的 ALS 患者进行了基于体素的形态计量学（VBM）和基于束的空间统计学（TBSS）分析。根据 D50 进展模型，26 名 b-ALS 和 52 名 l-ALS 患者亚组在疾病阶段或疾病侵袭性方面没有差异。VBM 分析显示灰质和白质中存在广泛的 ALS 相关变化，b-ALS 更为明显。TBSS 分析显示 b-ALS 主要表现为额部各向异性分数降低。这表明与 l-ALS 相比，b-ALS 患者组的神经退行性负担程度更高。相应地，球部症状负担越高，与右侧颞叶和下额叶灰质密度降低以及半球间和长联合束的各向异性分数降低相关。患者在 I 期和 II 期之间的对比进一步表明，b-ALS 的特征是早期皮质病理学，并且仅在原发性运动区之外扩展到额部和颞部区域。相比之下，l-ALS 在 II 期之前一直表现出原发性运动区内部结构完整性的持续丧失。因此，我们为 ALS 研究中分别治疗两种发病类型提供了强有力的理由。
