Department of Anatomy and Neurosciences, VUmc MS Center Amsterdam, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, The Netherlands.
J Neurol Neurosurg Psychiatry. 2018 Feb;89(2):205-210. doi: 10.1136/jnnp-2017-316329. Epub 2017 Oct 6.
Functional connectivity is known to increase as well as decrease throughout the brain in multiple sclerosis (MS), which could represent different stages of the disease. In addition, functional connectivity changes could follow the atrophy pattern observed with disease progression, that is, moving from the deep grey matter towards the cortex. This study investigated when and where connectivity changes develop and explored their clinical and cognitive relevance across different MS stages.
A cohort of 121 patients with early relapsing-remitting MS (RRMS), 122 with late RRMS and 53 with secondary progressive MS (SPMS) as well as 96 healthy controls underwent MRI and neuropsychological testing. Functional connectivity changes were investigated for (1) within deep grey matter connectivity, (2) connectivity between the deep grey matter and cortex and (3) within-cortex connectivity. A post hoc regional analysis was performed to identify which regions were driving the connectivity changes.
Patients with late RRMS and SPMS showed increased connectivity of the deep grey matter, especially of the putamen and palladium, with other deep grey matter structures and with the cortex. Within-cortex connectivity was decreased, especially for temporal, occipital and frontal regions, but only in SPMS relative to early RRMS. Deep grey matter connectivity alterations were related to cognition and disability, whereas within-cortex connectivity was only related to disability.
Increased connectivity of the deep grey matter became apparent in late RRMS and further increased in SPMS. The additive effect of cortical network degeneration, which was only seen in SPMS, may explain the sudden clinical deterioration characteristic to this phase of the disease.
已知在多发性硬化症（MS）中，大脑的功能连接既会增加也会减少，这可能代表疾病的不同阶段。此外，功能连接的变化可能会跟随疾病进展中观察到的萎缩模式，即从深部灰质向皮层移动。本研究调查了连接变化何时何地发生，并探讨了它们在不同 MS 阶段的临床和认知相关性。
一组 121 例早期复发缓解型多发性硬化症（RRMS）患者、122 例晚期 RRMS 患者和 53 例继发进展型多发性硬化症（SPMS）患者以及 96 名健康对照者接受了 MRI 和神经心理学测试。研究了（1）深部灰质内连接、（2）深部灰质与皮层之间的连接和（3）皮层内连接的功能连接变化。进行了事后区域分析，以确定哪些区域驱动了连接变化。
晚期 RRMS 和 SPMS 患者的深部灰质连接增加，尤其是壳核和苍白球与其他深部灰质结构和皮层的连接增加。皮层内连接减少，尤其是颞叶、枕叶和额叶，但仅在 SPMS 中与早期 RRMS 相比。深部灰质连接改变与认知和残疾有关，而皮层内连接仅与残疾有关。
晚期 RRMS 深部灰质连接增加，在 SPMS 中进一步增加。皮层网络退化的附加效应仅在 SPMS 中可见，这可能解释了该疾病阶段的突然临床恶化特征。
