C9ORF72 and the FTD-ALS spectrum: a systematic review of neuroimaging studies

ABSTRACT OBJECTIVE: To perform a systematic review of the literature on the neuroimaging investigation of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) associated with C9ORF72 mutation. METHODS: The search was performed on PubMed and LILACS with the following terms:C9ORF72, MRI, SPECT, PET, ALS, FTD. No filters were added. RESULTS Twenty articles were selected. Most studies found consistent involvement of frontotemporal regions in C9ORF72 carriers, including prefrontal cortex, and also cingulate, subcortical regions, especially the thalami, and posterior regions such as the parietal and occipital lobes. Functional connectivity was also explored and impaired sensorimotor connectivity in striatum and thalami was found in behavioral variant FTDC9ORF72 carriers. Some papers have reported an absence of significant abnormalities on brain imaging. CONCLUSION The inclusion of patients at different stages of the disease, differences in neuroimaging methods across studies, and distinct clinical phenotypes associated with C9ORF72 may account for the heterogeneity of results.

摘要

研究目的：针对携带C9ORF72突变的额颞叶痴呆（frontotemporal dementia, FTD）与肌萎缩侧索硬化（amyotrophic lateral sclerosis, ALS）的神经影像学相关研究文献开展系统综述。

研究方法：在PubMed及LILACS数据库中进行文献检索，检索词设置为C9ORF72、MRI、SPECT、PET、ALS、FTD，未添加任何筛选条件。

研究结果：最终纳入20篇相关文献。多数研究发现，C9ORF72突变携带者的额颞叶区域存在一致性受累，涵盖前额叶皮层、扣带回及皮层下区域（尤以丘脑最为显著），同时累及顶叶、枕叶等后部脑区。另有研究对功能连接进行了探索，结果显示携带C9ORF72突变的行为变异型FTD患者存在纹状体与丘脑的感觉运动连接受损。部分研究则报告脑部影像学未出现显著异常。

研究结论：纳入患者的疾病分期存在差异、不同研究间所采用的神经影像学方法各不相同，以及C9ORF72突变相关的临床表型存在区别，上述因素或可解释研究结果的异质性。