塩浜 直

BACKGROUND: Rett syndrome is a genetic neurodevelopmental disorder that predominantly affects girls. While microcephaly is a common feature, there is limited information on the detailed structural changes in the brain. This study aimed to identify regional brain volume abnormalities and explore the correlation between brain volume and clinical characteristics. METHODS: We compared the regional brain volumes of 20 female children with Rett syndrome to those of 25 healthy female children. Additionally, we assessed the correlation between regional brain volume, Clinical Severity Scores, and epilepsy status. RESULTS: Significantly smaller volumes were observed in all brain regions, including the cerebral cortex, cerebral white matter, subcortical gray matter, cerebellum, and brainstem. Within the cortical regions, volume reduction was prominent in the left precentral, right lateral occipital, left precuneus, left inferior parietal, and right medial orbitofrontal cortices. After correcting for intracranial volumes, volume reduction was more prominent in the cerebral cortices than in the cerebral white matter. Small volumes were consistently observed, regardless of age. Negative correlations were observed between the volumes of multiple regions and the Clinical Severity Scores. There were no correlations among regional brain volume, seizure control, or duration of epilepsy. CONCLUSION: The mechanism underlying the cortical-dominant volume reduction remains unclear; however, it may be caused by altered synapse development associated with methyl-CpG-binding protein 2 gene abnormalities. Characteristic impairments in visual recognition and deterioration of motor function in Rett syndrome may be associated with significant volume reduction in specific cortical regions, such as the lateral occipital cortex, precuneus, and precentral gyrus.

Autism spectrum disorder is a neurodevelopmental condition characterized by reduced social communication and repetitive behaviors. Altered neurogenesis, including disturbed neuronal migration, has been implicated in autism spectrum disorder. Using diffusion MRI, we previously identified neuronal migration pathways in the human fetal brain and hypothesized that similar pathways persist into adulthood, with differences in volume and microstructural characteristics between individuals with autism spectrum disorder and controls. We analyzed diffusion MRI-based tractography of subventricular zone-related pathways in 15 young adult men with autism spectrum disorder and 18 controls at Massachusetts General Hospital, with validation through the Autism Imaging Data Exchange II dataset. Participants with autism spectrum disorder had reduced subventricular zone pathway volumes and fractional anisotropy compared to controls. Furthermore, subventricular zone pathway volume was positively correlated (r: 0.68; 95% CI: 0.25 to 0.88) with symptom severity, suggesting that individuals with more severe symptoms tended to have larger subventricular zone pathway volumes, normalized by brain size. Analysis of the Autism Imaging Data Exchange cohort confirmed these findings of reduced subventricular zone pathway volumes in autism spectrum disorder. While some of these pathways may potentially include inaccurately disconnected pathways that go through the subventricular zone, our results suggest that diffusion MRI-based tractography pathways anatomically linked to the periventricular region are associated with certain symptom types in adult males with autism spectrum disorder.

Drug-induced gingival overgrowth is associated with various systemic diseases, including epilepsy. Among antiepileptic medications, phenytoin is commonly reported to cause this condition. In contrast, sodium valproate (VPA), another widely used antiepileptic drug, rarely induces gingival overgrowth. This difference in side effects highlights the variability in drug-induced oral complications among different antiepileptic medications. This case study presents a patient who developed significant gingival overgrowth after using VPA for over 10 years. The study aims to identify VPA as the causative agent and observe changes during long-term administration and after dose reduction. Our findings demonstrate that even long-standing gingival overgrowth can improve rapidly following discontinuation of the causative medication, providing valuable insights for managing similar cases in the future.

Mutations in TSC1 or TSC2 in axons induce tuberous sclerosis complex. Neurological manifestations mainly include epilepsy and autism spectrum disorder (ASD). ASD is the presenting symptom (25-50% of patients). ASD was observed at significantly higher frequencies in participants with TSC2 than those with TSC1 mutations. The occurrence of TSC2 mutations is about 50% larger than TSC1. Therefore, ASD may develop due to TSC2 deficiency. TSC2 regulates microRNA biogenesis and Microprocessor activity via GSK3β. Of reference, everolimus has the best treatment target because of the higher potency of interactions with mTORC2 rather than rapamycin. Mutations in the TSC1 and TSC2 genes result in the constitutive hyperactivation of the mammalian target of the rapamycin (mTOR) pathway, contributing to the growth of benign tumors or hamartomas in various organs. TSC2 mutations were associated with a more severe phenotypic spectrum than TSC1 mutations because of the inhibition of the mTOR cascade. There are few studies on the peptide analysis of this disorder in relation to everolimus. Only one study reported that, in ten plasma samples, pre-melanosome protein (PMEL) and S-adenosylmethionine (SAM) were significantly changed as diagnostic prognostic effects. Our study on peptide analysis in Protosera Inc (Osaka, Japan) revealed that three peptides that were related to inflammation in two patients with tuberous sclerosis, who showed a 30% decrease in ASD symptoms following everolimus treatment. TSC2 mutations were associated with a more severe phenotypic spectrum due to the inhibition of the mTOR cascade. PMEL and SAM were significantly changed as diagnostic effects.