Centre for the Research and Rehabilitation of Hereditary Ataxias, Libertad St 16 between 12 St & 16 St. 80100, Holguin, Cuba.
Cuban Centre for Neurosciences, 190 St, between 25 St & 27 St, 11300, Playa, Havana, Cuba.
Cerebellum. 2024 Oct;23(5):1839-1847. doi: 10.1007/s12311-024-01674-1. Epub 2024 Mar 4.
The influence of brain atrophy on sleep microstructure in Spinocerebellar Ataxias (SCAs) has not been extensively explored limiting the use of these sleep traits as surrogate biomarkers of neurodegeneration and clinical phenotype. The objective of the study is to explore the relationship between sleep microstructure and brain atrophy in SCA2 and its role in the clinical phenotype. Fourteen SCA2 mutation carriers (7 pre-manifest and 7 manifest subjects) underwent polysomnographic, structural MRI, and clinical assessments. Particularly, markers of REM and non-REM sleep microstructure, measures of cerebellar and brainstem atrophy, and clinical scores were analyzed through correlation and mediation analyses. The sleep spindle activity exhibited a negative correlation with the number of trials required to complete the verbal memory test (VMT), and a positive correlation with the cerebellar volume, but the significance of the latter correlation did not survive multiple testing corrections. However, the causal mediation analyses unveiled that sleep spindle activity significantly mediates the association between cerebellar atrophy and VMT performance. Regarding REM sleep, both phasic EMG activity and REM sleep without atonia exhibited significant associations with pontine atrophy and disease severity measures. However, they did not demonstrate a causal mediation effect between the atrophy measures and disease severity. Our study provides evidence about the association of the pontocerebellar atrophy with sleep microstructure in SCA2 offering insights into the cerebellar involvement in cognition via the control of the sleep spindle activity. Therefore, our findings may help to understand the disease pathogenesis and to better characterize sleep microstructure parameters as disease biomarkers.Clinical trial registration number (TRN): No applicable.
小脑萎缩对脊髓小脑共济失调（SCA）睡眠微结构的影响尚未得到广泛探索，这限制了这些睡眠特征作为神经退行性变和临床表型替代生物标志物的应用。本研究旨在探讨 SCA2 睡眠微结构与脑萎缩之间的关系及其在临床表型中的作用。14 名 SCA2 基因突变携带者（7 名前发病和 7 名发病患者）接受了多导睡眠图、结构 MRI 和临床评估。特别是，通过相关性和中介分析，分析了 REM 和非 REM 睡眠微结构的标志物、小脑和脑干萎缩的测量值以及临床评分。睡眠纺锤波活动与完成言语记忆测试（VMT）所需的试验次数呈负相关，与小脑体积呈正相关，但后者的相关性在多重测试校正后不再显著。然而，因果中介分析显示，睡眠纺锤波活动显著介导了小脑萎缩与 VMT 表现之间的关联。关于 REM 睡眠，相位肌电图活动和 REM 睡眠无张力均与脑桥萎缩和疾病严重程度测量值显著相关。然而，它们在萎缩测量值和疾病严重程度之间没有表现出因果中介效应。我们的研究提供了 SCA2 中桥脑小脑萎缩与睡眠微结构之间关联的证据，深入了解了通过控制睡眠纺锤波活动小脑在认知中的参与。因此，我们的发现可能有助于了解疾病发病机制，并更好地将睡眠微结构参数作为疾病生物标志物进行特征描述。临床试验注册号（TRN）：无适用。
