Widespread grey matter pathology dominates the longitudinal cerebral MRI and clinical landscape of amyotrophic lateral sclerosis.
Widespread grey matter pathology dominates the longitudinal cerebral MRI and clinical landscape of amyotrophic lateral sclerosis.
复制标题
DOI：
10.1093/brain/awu162
复制
发表时间：
2014-09
期刊：
影响因子：
--
通讯作者：
Turner MR
中科院分区：
文献类型：
--
作者：
Menke RA;Körner S;Filippini N;Douaud G;Knight S;Talbot K;Turner MR
Menke/Koerner等人利用结构MRI探讨了肌萎缩侧索硬化症患者脑病理纵向变化的程度及其与临床特征的关系。横切面可见特征性白质束病理特征，而纵向上皮层受累占主导地位。这对诊断与治疗监测的生物标志物的发展具有重要意义。肌萎缩性侧索硬化症的诊断、分层和疾病进展监测目前依赖于临床病史和检查。肌萎缩性侧索硬化症的表型异质性，包括运动外认知障碍，现在已经得到了很好的认识。候选的生物标志物表现出不同的敏感性和特异性，研究主要是横断面进行的。60例散发性肌萎缩性侧索硬化症患者（无肌萎缩性侧索硬化症或痴呆家族史）在3 t时接受了基线多模态磁共振成像，通过基于体素的形态测量法分析t1加权图像来确定灰质病理。利用弥散张量成像得出的指标的基于束的空间统计分析来评估白质病理。横断面分析包括与健康对照组（n = 36）的组比较以及与临床特征的相关性，包括局部残疾、临床上运动神经元体征和认知障碍。对患者进行6个月的MRI随访，最后一次可用的扫描用于单独的纵向分析（n = 27）。在横断面研究中，白质病理的核心特征在皮质脊髓束和胼胝体中得到证实，并且与临床上运动神经元负荷密切相关，也与肢体残疾亚评分和进展率密切相关。局部灰质异常出现在左运动皮层与球功能障碍有关的地形适宜区域，以及与语言流畅性有关的布洛卡区及其同源区域。纵向分析揭示了灰质的进行性和广泛性变化，特别是基底节区。相比之下，白质病理进展有限，与先前未被认识到的个体临床上运动神经元评分的有限变化保持一致，尽管残疾进展。尽管横切面上发现一致的核心白质病理，但纵向上灰质病理占主导地位，包括临床沉默区域的进展，如基底节区，被认为反映了其更广泛的皮质连通性。这种变化在一系列明显的散发性患者中是显著的，而不是基因型特异性的影响。这也表明，肌萎缩侧索硬化症的上运动神经元病变可能在确定的症状期间相对恒定。这些发现对开发有效的诊断与治疗监测磁共振成像生物标志物具有重要意义。肌萎缩性侧索硬化症的最初特征可能是主要的白质束病理特征，演变为广泛的皮质网络变性。
Menke/Koerner et al. use structural MRI to explore the extent of longitudinal changes in cerebral pathology in amyotrophic lateral sclerosis, and their relationship to clinical features. A characteristic white matter tract pathological signature is seen cross-sectionally, while cortical involvement dominates longitudinally. This has implications for the development of biomarkers for diagnosis versus therapeutic monitoring. Diagnosis, stratification and monitoring of disease progression in amyotrophic lateral sclerosis currently rely on clinical history and examination. The phenotypic heterogeneity of amyotrophic lateral sclerosis, including extramotor cognitive impairments is now well recognized. Candidate biomarkers have shown variable sensitivity and specificity, and studies have been mainly undertaken only cross-sectionally. Sixty patients with sporadic amyotrophic lateral sclerosis (without a family history of amyotrophic lateral sclerosis or dementia) underwent baseline multimodal magnetic resonance imaging at 3 T. Grey matter pathology was identified through analysis of T1-weighted images using voxel-based morphometry. White matter pathology was assessed using tract-based spatial statistics analysis of indices derived from diffusion tensor imaging. Cross-sectional analyses included group comparison with a group of healthy controls (n = 36) and correlations with clinical features, including regional disability, clinical upper motor neuron signs and cognitive impairment. Patients were offered 6-monthly follow-up MRI, and the last available scan was used for a separate longitudinal analysis (n = 27). In cross-sectional study, the core signature of white matter pathology was confirmed within the corticospinal tract and callosal body, and linked strongly to clinical upper motor neuron burden, but also to limb disability subscore and progression rate. Localized grey matter abnormalities were detected in a topographically appropriate region of the left motor cortex in relation to bulbar disability, and in Broca’s area and its homologue in relation to verbal fluency. Longitudinal analysis revealed progressive and widespread changes in the grey matter, notably including the basal ganglia. In contrast there was limited white matter pathology progression, in keeping with a previously unrecognized limited change in individual clinical upper motor neuron scores, despite advancing disability. Although a consistent core white matter pathology was found cross-sectionally, grey matter pathology was dominant longitudinally, and included progression in clinically silent areas such as the basal ganglia, believed to reflect their wider cortical connectivity. Such changes were significant across a range of apparently sporadic patients rather than being a genotype-specific effect. It is also suggested that the upper motor neuron lesion in amyotrophic lateral sclerosis may be relatively constant during the established symptomatic period. These findings have implications for the development of effective diagnostic versus therapeutic monitoring magnetic resonance imaging biomarkers. Amyotrophic lateral sclerosis may be characterized initially by a predominantly white matter tract pathological signature, evolving as a widespread cortical network degeneration.
登录
查看更多内容
影响因子：
4.4
作者：
Cedarbaum, JM;Stambler, N;Nakanishi, A
通讯作者：
Nakanishi, A
影响因子：
14.5
作者：
Douaud, Gwenaelle;Filippini, Nicola;Turner, Martin R.
通讯作者：
Turner, Martin R.
影响因子：
4.8
作者：
Agosta, Federica;Galantucci, Sebastiano;Filippi, Massimo
通讯作者：
Filippi, Massimo
影响因子：
--
作者：
Blain, Camilla R. V.;Williams, Victoria C.;Simmons, Andy
通讯作者：
Simmons, Andy
影响因子：
14.5
作者：
Abrahams, S;Goldstein, LH;Leigh, PN
通讯作者：
Leigh, PN