The University of Tokyo · Medicine
Professor Masashi Mizuguchi's research lab specializes in pediatric neurology and neuropathology, focusing on the mechanisms, clinical features, and molecular pathology of acute encephalopathies and neurodevelopmental disorders. The lab investigates rare and severe brain disorders such as acute necrotizing encephalopathy of childhood, tuberous sclerosis complex (TSC), and neuronal migration disorders like Miller-Dieker syndrome. Using both clinical case studies and animal models—such as the Eker rat model of TSC—the lab explores the genetic, histological, and immunohistochemical underpinnings of these conditions, with translational goals in improving diagnosis, treatment, and outcomes. The lab also evaluates novel therapeutic approaches, including mTOR inhibitors like everolimus, for refractory seizures and behavioral symptoms in TSC patients.
Figures are computed from collected data and may differ slightly.
Acute encephalopathy is the most serious complication of pediatric viral infections, such as influenza and exanthem subitum. It occurs worldwide, but is most prevalent in East Asia, and every year several hundreds of Japanese children are affected by influenza-associated encephalopathy. Mortality has recently declined, but is still high. Many survivors are left with motor and intellectual disabilities, and some with epilepsy. This article reviews various syndromes of acute encephalopathy by clas
The clinicopathological features of a previously unrecognised type of acute encephalopathy prevalent among Japanese children is described by reviewing the records of 13 consecutive patients treated and 28 previously reported cases. The hallmark of this encephalopathy, proposed to be a novel entity termed acute necrotising encephalopathy of childhood, is multiple, necrotic brain lesions showing a symmetric distribution. The encephalopathy was noted in previously healthy children after respiratory
Adjunctive everolimus treatment improved seizure frequency with a tolerable safety relative to placebo among 35 Japanese patients with TSC-associated refractory seizures, consistent with the results of overall EXIST-3 study involving 366 patients. A favorable trend towards the improvement of ASD symptoms was observed.
The Eker rat is a model for human tuberous sclerosis (TSC) caused by a mutation in the Tsc2 gene. We describe here histological and immunohistochemical findings of the brain lesions in Eker rats, with emphasis on 2 novel lesions found in this study: a cortical tuber and an anaplastic ganglioglioma. The rat cortical tuber resembled those of humans, and further confirmed the value of this animal model as a tool for investigating the molecular pathology of tuberous sclerosis. On the other hand, the
Influenza is occasionally complicated by CNS disorders, in particular impairment of consciousness. Severe disorders encompass multiple, distinct syndromes manifesting acute encephalopathy, whereas mild disorders represent multiple, ill-defined neuropsychiatric syndromes. Acute encephalopathy is manifested with seizures and coma, with or without multi-organ involvement. The outcome varies from death or neurologic sequelae to recovery and differs among syndromes. Transient neuropsychiatric disorde
The Miller-Dieker syndrome, a disorder of neuronal migration, is caused by deletions of chromosome 17p13.3. Recently, a gene on 17p13.3, named LIS-1, was identified as the causative gene for this cerebral anomaly. Here we immunochemically and immunohistochemically localized the gene product, LIS-1 protein, among control normal subjects and patients with Miller-Dieker syndrome, using specific antibodies raised against synthetic peptide fragments of LIS-1 protein. Western blot analyses identified
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