Hocking Darren R, Loesch Danuta Z, Trost Nicholas, Bui Minh Q, Hammersley Eleanor, Francis David, Tassone Flora, Storey Elsdon
Developmental Neuromotor and Cognition Lab, School of Psychology and Public Health, La Trobe University, Melbourne, VIC, Australia.
School of Psychology and Public Health, La Trobe University, Melbourne, VIC, Australia.
Front Neurol. 2019 Aug 13;10:832. doi: 10.3389/fneur.2019.00832. eCollection 2019.
This study explores the relationships between hemispheric and cerebellar white matter lesions and motor and cognitive impairments in male carriers of Fragile-X Mental Retardation 1 () premutation alleles, and in a subgroup of these carriers affected with Fragile X-Associated Tremor/Ataxia syndrome (FXTAS). Regional and total white matter hyperintensities () on MRI, assessed using semiquantitative scores, were correlated with three motor rating scales (ICARS, UPDRS, Tremor), and neuropsychological measures of non-verbal reasoning, working memory and processing speed, in a sample of 30 male premutation carriers aged 39-81 years, and separately in a subsample of 17 of these carriers affected with FXTAS. There were significant relationships between in the infratentorial region and all three motor scales, as well as several cognitive measures-Prorated IQ, Matrix Reasoning, Similarities, and the Symbol Digit Modalities Test (SDMT), in the total sample of carriers, as well as in the FXTAS group separately. This shows that within the infratentorial region correlates across the categories of clinical status with a range of motor and cognitive impairments. In the FXTAS group, there was a highly significant relationship between supratentorial (periventricular) lesions and parkinsonism, and between both periventricular and supratentorial deep white matter and ICARS ataxia score. These findings further support the relevance of white matter changes in different brain regions to the motor and cognitive deficits across the spectrum of premutation involvement. Future longitudinal studies using larger sample sizes will be necessary to examine the factors that lead to conversion to a greater extent of neurological involvement as seen in the progression across the FXTAS spectrum.
本研究探讨了脆性X智力低下1（FMR1）前突变等位基因男性携带者以及其中患有脆性X相关震颤/共济失调综合征（FXTAS）的亚组中，半球和小脑白质病变与运动及认知障碍之间的关系。在30名年龄在39 - 81岁的男性前突变携带者样本中，以及在其中17名患有FXTAS的携带者子样本中，使用半定量评分评估的MRI上的区域和总白质高信号（WMH）与三个运动评定量表（ICARS、UPDRS、震颤）以及非言语推理、工作记忆和处理速度的神经心理学测量指标相关。在总携带者样本以及单独的FXTAS组中，幕下区域的WMH与所有三个运动量表以及几个认知测量指标——比例智商、矩阵推理、相似性和符号数字模态测验（SDMT）之间存在显著关系。这表明幕下区域内的WMH在临床状态类别中与一系列运动和认知障碍相关。在FXTAS组中，幕上（脑室周围）病变与帕金森症之间存在高度显著关系，脑室周围和幕上深部白质与ICARS共济失调评分之间也存在显著关系。这些发现进一步支持了不同脑区白质变化与前突变累及范围内的运动和认知缺陷的相关性。未来需要使用更大样本量的纵向研究来检查导致如FXTAS谱系进展中所见的更广泛神经受累转化的因素。
