Abstract：
FMR1 premutation carriers (55-200 CGG repeats) are at risk of developing fragile X-associated tremor/ataxia syndrome (FXTAS), a neurodegenerative disorder associated with motor and cognitive impairment. Bilateral hyperintensities of the middle cerebellar peduncles (MCP sign) are the major radiological hallmarks of FXTAS. In the general population, enlarged perivascular spaces (PVS) are biomarkers of small vessel disease and glymphatic dysfunction and are associated with cognitive decline. Our aim was to determine if premutation carriers show higher ratings of PVS than controls and whether enlarged PVS are associated with motor and cognitive impairment, MRI features of neurodegeneration, cerebrovascular risk factors and CGG repeat length. We evaluated 655 MRIs (1-10 visits/participant) from 229 carriers (164 with FXTAS and 65 without FXTAS) and 133 controls. PVS in the basal ganglia (BG-EPVS), centrum semiovale, and midbrain were evaluated with a semiquantitative scale. Mixed-effects models were used for statistical analysis adjusting for age. In carriers with FXTAS, we revealed that (1) BG-PVS ratings were higher than those of controls and carriers without FXTAS; (2) BG-PVS severity was associated with brain atrophy, white matter hyperintensities, enlarged ventricles, FXTAS stage and abnormal gait; (3) age-related increase in BG-PVS was associated with cognitive dysfunction; and (4) PVS ratings of all three regions showed robust associations with CGG repeat length and were higher in carriers with the MCP sign than carriers without the sign. This study demonstrates clinical relevance of PVS in FXTAS especially in the basal ganglia region and suggests microangiopathy and dysfunctional cerebrospinal fluid circulation in FXTAS physiopathology.
摘要：
FMR1前突变携带者（55-200个CGG重复序列）有发生脆性X相关震颤/共济失调综合征（FXTAS）的风险，一种与运动和认知障碍相关的神经退行性疾病。小脑中段的双侧高强度（MCP征）是FXTAS的主要放射学标志。在一般人群中,血管周围间隙增大(PVS)是小血管疾病和淋巴淋巴功能障碍的生物标志物,与认知功能下降相关.我们的目的是确定前突变携带者是否比对照组表现出更高的PVS评分，以及扩大的PVS是否与运动和认知障碍有关。神经变性的MRI特征，脑血管危险因素和CGG重复长度。我们评估了来自229个运营商（164个有FXTAS，65个没有FXTAS）和133个对照的655个MRI（1-10次访问/参与者）。基底神经节中的PVS（BG-EPVS），半谷中心,和中脑用半定量量表进行评估。使用混合效应模型进行年龄调整的统计分析。在使用FXTAS的运营商中，我们发现（1）BG-PVS评分高于对照组和无FXTAS的携带者；（2）BG-PVS严重程度与脑萎缩有关，白质高强度，扩大的心室，FXTAS阶段和异常步态；（3）BG-PVS的年龄相关增加与认知功能障碍有关；（4）所有三个区域的PVS评级均显示出与CGG重复长度的强关联，并且在具有MCP标志的携带者中高于没有该标志的携带者。这项研究证明了FXTAS中PVS的临床意义，尤其是在基底神经节区域，并提示FXTAS病理生理学中的微血管病和功能失调的脑脊液循环。
