Wirth Anna M, Khomenko Andrei, Baldaranov Dobri, Kobor Ines, Hsam Ohnmar, Grimm Thomas, Johannesen Siw, Bruun Tim-Henrik, Schulte-Mattler Wilhelm, Greenlee Mark W, Bogdahn Ulrich
Department of Neurology, University Hospital of Regensburg, Regensburg, Germany.
Department of Experimental Psychology, University of Regensburg, Regensburg, Germany.
Front Neurol. 2018 Jul 30;9:614. doi: 10.3389/fneur.2018.00614. eCollection 2018.
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative process affecting upper and lower motor neurons as well as non-motor systems. In this study, precentral and postcentral cortical thinning detected by structural magnetic resonance imaging (MRI) were combined with clinical (ALS-specific functional rating scale revised, ALSFRS-R) and neurophysiological (motor unit number index, MUNIX) biomarkers in both cross-sectional and longitudinal analyses. The unicenter sample included 20 limb-onset classical ALS patients compared to 30 age-related healthy controls. ALS patients were treated with standard Riluzole and additional long-term G-CSF (Filgrastim) on a named patient basis after written informed consent. Combinatory biomarker use included cortical thickness of atlas-based dorsal and ventral subdivisions of the precentral and postcentral cortex, ALSFRS-R, and MUNIX for the musculus abductor digiti minimi (ADM) bilaterally. Individual cross-sectional analysis investigated individual cortical thinning in ALS patients compared to age-related healthy controls in the context of state of disease at initial MRI scan. Beyond correlation analysis of biomarkers at cross-sectional group level ( = 20), longitudinal monitoring in a subset of slow progressive ALS patients ( = 4) explored within-subject temporal dynamics of repeatedly assessed biomarkers in time courses over at least 18 months. Cross-sectional analysis demonstrated individually variable states of cortical thinning, which was most pronounced in the ventral section of the precentral cortex. Correlations of ALSFRS-R with cortical thickness and MUNIX were detected. Individual longitudinal biomarker monitoring in four slow progressive ALS patients revealed evident differences in individual disease courses and temporal dynamics of the biomarkers. A combinatory use of structural MRI, neurophysiological and clinical biomarkers allows for an appropriate and detailed assessment of clinical state and course of disease of ALS.
肌萎缩侧索硬化症（ALS）是一种进行性神经退行性病变，会影响上下运动神经元以及非运动系统。在本研究中，通过结构磁共振成像（MRI）检测到的中央前回和中央后回皮质变薄，与临床（修订的ALS特异性功能评定量表，ALSFRS-R）和神经生理学（运动单位数量指数，MUNIX）生物标志物相结合，进行横断面和纵向分析。单中心样本包括20例肢体起病的经典ALS患者，与30例年龄匹配的健康对照者进行比较。在获得书面知情同意后，ALS患者在指定患者基础上接受标准利鲁唑治疗以及额外的长期粒细胞集落刺激因子（非格司亭）治疗。联合使用的生物标志物包括基于图谱的中央前回和中央后回皮质背侧和腹侧分区的皮质厚度、ALSFRS-R以及双侧小指展肌（ADM）的MUNIX。个体横断面分析研究了在初次MRI扫描时疾病状态背景下，与年龄匹配的健康对照者相比，ALS患者个体的皮质变薄情况。除了横断面组水平（n = 20）的生物标志物相关性分析外，对一部分缓慢进展性ALS患者（n = 4）进行的纵向监测，探讨了在至少18个月的时间进程中反复评估的生物标志物的个体内时间动态变化。横断面分析显示皮质变薄的个体状态存在差异，在中央前回皮质腹侧最为明显。检测到ALSFRS-R与皮质厚度和MUNIX之间存在相关性。对四名缓慢进展性ALS患者进行的个体纵向生物标志物监测显示，个体病程和生物标志物的时间动态变化存在明显差异。结构MRI、神经生理学和临床生物标志物的联合使用，能够对ALS的临床状态和病程进行适当而详细的评估
