AUTHOR=Kong Yu , Li Qiu-bo , Yuan Zhao-hong , Jiang Xiu-fang , Zhang Gu-qing , Cheng Nan , Dang Na 

TITLE=Multimodal Neuroimaging in Rett Syndrome With MECP2 Mutation

JOURNAL=Frontiers in Neurology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2022.838206

DOI=10.3389/fneur.2022.838206

ISSN=1664-2295

ABSTRACT=Rett syndrome (RTT) is a rare neurodevelopmental disorder characterized by severe cognitive, social, and physical impairments resulting from de novo mutations in the X-chromosomal methyl-CpG binding protein gene 2 (MECP2). While there is still no cure for RTT, exploring up to date neuro-functional diagnostic markers, discovering new potential therapeutic targets and searching for novel drug efficacy evaluation indicators is fundamental. Multiple neuroimaging studies of brain structure and function have been carried out in RTT-linked gene mutation carriers in order to unravel disease-specific imaging features and explore genotype-phenotype associations. Here, we reviewed neuroimaging literature on this disorder. Magnetic resonance imaging (MRI) morphologic imaging studies have shown global atrophy of gray and white matter and regional variations in brain maturation. Diffusion tensor imaging (DTI) studies have demonstrated reduced fractional anisotropy (FA) in left peripheral white matter areas, left major white matter tracts, and cingulum bilaterally and white matter microstructural/network topology changes have been further found to correlate with behavioral abnormalities in RTT. Cerebral blood perfusion imaging studies performed using single-photon emission computed tomography (SPECT) or positron emission tomography (PET) have evidenced decreased global cerebral blood flow (CBF), particularly in prefrontal and temporoparietal areas, while magnetic resonance spectroscopy (MRS) and PET studies have contributed to unravel metabolism alterations in RTT patients. Results from available reports confirm that multimodal neuroimaging can provide new insights into the complex interplay between genes, neurotransmitter pathways abnormalities, disease-related behaviors and clinical severity. However, common limitations of the available studies include small sample sizes and hypothesis-based, regional specific approaches. We therefore conclude that the field is still in its early development phase and that multi-modal/multi-sequences studies with improved post-processing technologies as well as combined PET-MRI approaches are urgently needed to further explore RTT brain alterations.