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 neurofunctional diagnostic markers, discovering new potential therapeutic targets, and searching for novel drug efficacy evaluation indicators are fundamental. Multiple neuroimaging studies on brain structure and function have been carried out in RTT-linked gene mutation carriers to unravel disease-specific imaging features and explore genotype-phenotype associations. Here, we reviewed the neuroimaging literature on this disorder. MRI morphologic studies have shown global atrophy of gray matter (GM) and white matter (WM) and regional variations in brain maturation. Diffusion tensor imaging (DTI) studies have demonstrated reduced fractional anisotropy (FA) in left peripheral WM areas, left major WM tracts, and cingulum bilaterally, and WM microstructural/network topology changes have been further found to be correlated with behavioral abnormalities in RTT. Cerebral blood perfusion imaging studies using single-photon emission CT (SPECT) or PET have evidenced a decreased global cerebral blood flow (CBF), particularly in prefrontal and temporoparietal areas, while magnetic resonance spectroscopy (MRS) and PET studies have contributed to unraveling metabolic alterations in patients with RTT. The results obtained from the available reports confirm that multimodal neuroimaging can provide new insights into a complex interplay between genes, neurotransmitter pathway abnormalities, disease-related behaviors, and clinical severity. However, common limitations related to the available studies include small sample sizes and hypothesis-based and region-specific approaches. We, therefore, conclude that this field is still in its early development phase and that multimodal/multisequence studies with improved post-processing technologies as well as combined PET–MRI approaches are urgently needed to further explore RTT brain alterations.

Tubulin plays an essential role in cortical development, and TUBA1A encodes a major neuronal α-tubulin. Neonatal mutations in TUBA1A are associated with severe brain malformations, and approximately 70% of patients with reported cases of TUBA1A mutations exhibit lissencephaly. We report the case of a 1-year-old boy with the TUBA1A nascent mutation c.1204C >T, p.Arg402Cys, resulting in lissencephaly, developmental delay, and seizures, with a brain MRI showing normal cortical formation in the bilateral frontal lobes, smooth temporo-parieto-occipital gyri and shallow sulcus. This case has not been described in any previous report; thus, the present case provides new insights into the broad disease phenotype and diagnosis associated with TUBA1A mutations. In addition, we have summarized the gene mutation sites, neuroradiological findings, and clinical details of cases previously described in the literature and discussed the differences that exist between individual cases of TUBA1A mutations through a longitudinal comparative analysis of similar cases. The complexity of the disease is revealed, and the importance of confirming the genetic diagnosis from the beginning of the disease is emphasized, which can effectively shorten the diagnostic delay and help clinicians provide genetic and therapeutic counseling.

To investigate the ability of a multidisciplinary approach that combines multimodal neuroimaging with video-electroencephalography (v-EEG) to predict post-surgical outcomes in patients with intractable epilepsy, and explore prognostic predictors for these patients. Fifty-eight patients with intractable epilepsy who underwent surgery between March 2016 and October 2019 were reviewed retrospectively. Demographic, clinical, v-EEG, neuroimaging, surgical, and regular follow-up seizure outcome data were collected. Forty-six patients with a follow-up of at least 12 months were graded by Engel scores. Univariate and multivariate analyses were applied to explore prognostic factors that could predict post-surgical seizure outcomes. Of the 58 patients, 28 were males. The median age was 27 years, the median age at first seizure was 11 years, and the median duration of seizures was 10 years. The Kaplan-Meier log-rank test showed that regardless of whether the follow-up duration was considered, epilepsy type, v-EEG, PET/CT, image post-processing methods, and a multidisciplinary approach that combined multimodal imaging with v-EEG were all correlated with seizure outcomes. Multivariate analysis found that the multidisciplinary approach was an independent predictor of post-surgical outcomes in patients with intractable epilepsy (hazard ratio = 11.400, 95% confidence interval = 2.249-57.787, p=0.003). The present study showed that the multidisciplinary approach could provide independent prognostic information for patients with intractable epilepsy undergoing surgery. This approach has strong potential for the easier selection of patients to undergo surgical treatment and accurate prognostication.

To investigate the application value of multimodal MRI combined with PET metabolic parameters in detecting temporal lobe epilepsy (TLE) with dual pathology (DP) and the prediction effect of post-surgical outcomes in these patients. We retrospectively reviewed 50 patients with TLE-DP who underwent surgery at our hospital between January 2016 and December 2021 and collected the demographics, clinical characteristics, video-electroencephalography (v-EEG), neuroimaging, and surgical data. Seizure outcome data were collected during a regular follow-up of at least 12 months and were graded using Engel scores. Fisher's exact test was used to compare the differences in DP detection rates of various diagnostic modalities. Univariate and multivariate analyses were performed to explore the prognostic factors for predicting seizure outcomes post-surgery. Of the 50 patients, 20 were males. The median age was 30, the median age at first seizure was 14, and the median duration was ten years. Voxel-based morphometry-PET statistical parametric mapping-PET/MRI (VBM-PSPM-PET/MRI) had the highest detection rate, followed by PET/MRI, VBM analysis, and PET-SPM. Regardless of follow-up duration, v-EEG, PET, image post-processing methods, and VBM-PSPM-PET/MRI statistically correlated with seizure outcomes using the log-rank test in the Kaplan-Meier analysis. Multivariate analysis showed that VBM-PSPM-PET/MRI was an independent predictor of TLE-DP (hazard ratio (HR) = 15.674, 95 % CI = 0.002-0.122, P < 0.00 1). Our study illustrates that VBM-PSPM-PET/MRI has the highest detection value in patients with TLE-DP and can provide independent prognostic information for patients who undergo surgery. This approach has the most substantial potential for the selection of candidates for patients who undergo surgical treatment and for prognostic stratification.

Essential tremor (ET) and Parkinson's disease (PD) are common chronic movement disorders that can cause a substantial degree of disability. However, the etiology underlying these two conditions remains poorly understood. In the present study, Whole‑exome sequencing of peripheral blood samples from the proband and Sanger sequencing of the other 18 family members, and pedigree analysis of four generations of 29 individuals with both ET and PD in a nonconsanguineous Chinese family were performed. Specifically, family members who had available medical information, including historical documentation and physical examination records, were included. A novel c.1909A>T (p.Ser637Cys) missense mutation was identified in the eukaryotic translation initiation factor 4γ1 (EIF4G1) gene as the candidate likely responsible for both conditions. In total, 9 family members exhibited tremor of the bilateral upper limbs and/or head starting from ages of ≥40 years, 3 of whom began showing evidence of PD in their 70s. Eukaryotic initiation factor 4 (eIF4)G1, a component of the translation initiation complex eIF4F, serves as a scaffold protein that interacts with many initiation factors and then binds to the 40S ribosomal subunit. The EIF4G1 (p.Ser637Cys) might inhibit the recruitment of the mRNA to the ribosome. In conclusion, the results from the present study suggested that EIF4G1 may be responsible for the hereditary PD with ‘antecedent ET’ reported in the family assessed.