Computational Neuroimaging Group, Biomedical Sciences Institute, Trinity College Dublin, Ireland.
Computational Neuroimaging Group, Biomedical Sciences Institute, Trinity College Dublin, Ireland; Department of Neurology, Aeginition Hospital, University of Athens, Greece.
Neuroimage Clin. 2020;27:102300. doi: 10.1016/j.nicl.2020.102300. Epub 2020 May 30.
The thalamus is a key cerebral hub relaying a multitude of corticoefferent and corticoafferent connections and mediating distinct extrapyramidal, sensory, cognitive and behavioural functions. While the thalamus consists of dozens of anatomically well-defined nuclei with distinctive physiological roles, existing imaging studies in motor neuron diseases typically evaluate the thalamus as a single structure. Based on the unique cortical signatures observed in ALS and PLS, we hypothesised that similarly focal thalamic involvement may be observed if the nuclei are individually evaluated. A prospective imaging study was undertaken with 100 patients with ALS, 33 patients with PLS and 117 healthy controls to characterise the integrity of thalamic nuclei. ALS patients were further stratified for the presence of GGGGCC hexanucleotide repeat expansions in C9orf72. The thalamus was segmented into individual nuclei to examine their volumetric profile. Additionally, thalamic shape deformations were evaluated by vertex analyses and focal density alterations were examined by region-of-interest morphometry. Our data indicate that C9orf72 negative ALS patients and PLS patients exhibit ventral lateral and ventral anterior involvement, consistent with the 'motor' thalamus. Degeneration of the sensory nuclei was also detected in C9orf72 negative ALS and PLS. Both ALS groups and the PLS cohort showed focal changes in the mediodorsal-paratenial-reuniens nuclei, which mediate memory and executive functions. PLS patients exhibited distinctive thalamic changes with marked pulvinar and lateral geniculate atrophy compared to both controls and C9orf72 negative ALS. The considerable ventral lateral and ventral anterior pathology detected in both ALS and PLS support the emerging literature of extrapyramidal dysfunction in MND. The involvement of sensory nuclei is consistent with sporadic reports of sensory impairment in MND. The unique thalamic signature of PLS is in line with the distinctive clinical features of the phenotype. Our data confirm phenotype-specific patterns of thalamus involvement in motor neuron diseases with the preferential involvement of nuclei mediating motor and cognitive functions. Given the selective involvement of thalamic nuclei in ALS and PLS, future biomarker and natural history studies in MND should evaluate individual thalamic regions instead overall thalamic changes.
丘脑是大脑的一个关键中枢，它传递着大量皮质传出和皮质传入的连接，并介导独特的锥体外系、感觉、认知和行为功能。虽然丘脑由数十个解剖上定义明确、具有独特生理作用的核组成，但现有的运动神经元疾病的影像学研究通常将丘脑作为一个单一的结构进行评估。基于在 ALS 和 PLS 中观察到的独特皮质特征，我们假设如果单独评估核，可能会观察到类似的焦点丘脑受累。一项前瞻性影像学研究纳入了 100 例 ALS 患者、33 例 PLS 患者和 117 例健康对照者，以描述丘脑核的完整性。ALS 患者进一步根据 C9orf72 中 GGGGCC 六核苷酸重复扩展的存在进行分层。将丘脑分割成单独的核以检查其体积分布。此外，通过顶点分析评估丘脑形状变形，并通过感兴趣区形态计量学检查焦点密度改变。我们的数据表明，C9orf72 阴性 ALS 患者和 PLS 患者表现出腹外侧和腹前受累，与“运动”丘脑一致。在 C9orf72 阴性 ALS 和 PLS 中也检测到感觉核的变性。两组 ALS 患者和 PLS 队列均显示出介导记忆和执行功能的中背-旁前- reunien 核的焦点变化。与对照组和 C9orf72 阴性 ALS 相比，PLS 患者的丘脑变化明显，表现为明显的丘脑枕和外侧膝状体萎缩。在 ALS 和 PLS 中检测到的相当大的腹外侧和腹前病理学支持 MND 中锥体外系功能障碍的新兴文献。感觉核的受累与 MND 中感觉障碍的散发性报告一致。PLS 的独特丘脑特征与表型的独特临床特征一致。我们的数据证实了运动神经元疾病中丘脑受累的表型特异性模式，优先涉及介导运动和认知功能的核。鉴于 ALS 和 PLS 中丘脑核的选择性受累，MND 中的未来生物标志物和自然史研究应评估单个丘脑区域，而不是整体丘脑变化。
