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

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 FTD C9ORF72 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.