von Hippel-Lindau (VHL) disease is a hereditary tumor disease in which tumors develop in multiple organs, not only as hemangioblastomas (HBs) in the central nervous system, but also as kidney tumors, pheochromocytomas, and so on. Much about the epidemiology of VHL disease remained unknown until fairly recently in Japan, leading to calls for the establishment of a VHL disease epidemiological database in Japanese. To elucidate its epidemiology in Japan, the Japanese Ministry of Health, Labour and Welfare created the VHL Disease Study Group, which was put in charge of carrying out a nationwide epidemiological survey. The survey found close to 400 Japanese VHL disease patients throughout the country. Based on those results, the VHL Disease Study Group created the VHL Disease Treatment Guideline and also a severity classification. It is thought that the prognosis of VHL disease patients can be improved by performing genetic diagnosis and careful follow-up. Accordingly, the University of Tokyo Hospital put in place an in-hospital system for implementing genomic medicine for VHL disease based on genetic diagnosis. For that system, it was especially important to establish (I) accurate genetic diagnostic techniques, (II) genetic counseling capabilities for the patients and their families, and (III) a system of cooperation among multiple departments, including urology departments, and so on. Further elucidation of the epidemiology and the development of genomic medicine are needed to improve the treatment results of VHL disease in Japan.
The number of clinical research papers published worldwide on moyamoya disease (MMD) has increased recently. However, the majority of the literature comprises retrospective single-center studies collecting data on small numbers of patients. Several multi-center studies are ongoing in Japan; however, the current data are insufficient for comprehensively outlining the various characteristics of MMD. To enhance our knowledge on epidemiologic, vascular, and genetic aspects of MMD, a prospective multicenter registry will be established in Japan that will help to streamline clinical research as well as improve clinical treatments and long-term outcomes. Patients with MMD or secondary moyamoya syndrome referred to the participating centers will be invited to the registry. Demographic and physiological parameters, along with neuroimaging data will be collected chronologically. Clinical events, including neurological, medical, and surgical interventions will be recorded. Whole blood samples will be collected. Extra- and intra-cranial vascular tissue, and/or cerebrospinal fluid will also be collected from patients who undergo surgical revascularization. These biospecimens will be stored at the repositories and utilized for genome-wide association studies for identifying genetic variants, as well as tissue-specific proteomic, and/or molecular analyses. Ethics approval will be obtained at all facilities collecting biospecimens. The registry will provide descriptive statistics on functional outcomes, surgical techniques used, medications, and neurological events stratified according to patients’ clinical characteristics. We expect this study to provide novel insights in the management of MMD patients and design better therapies.
Traumatic brain injury (TBI) is the leading cause of death and disability in children. Pediatric TBI is associated with several distinctive characteristics that differ from adults and are attributable to age-related anatomical and physiological differences, pattern of injuries based on the physical ability of the child, and difficulty in neurological evaluation in children. Evidence suggests that children exhibit a specific pathological response to TBI with distinct accompanying neurological symptoms, and considerable efforts have been made to elucidate their pathophysiology. In addition, recent technical advances in diagnostic imaging of pediatric TBI has facilitated accurate diagnosis, appropriate treatment, prevention of complications, and helped predict long-term outcomes. Here a review of recent studies relevant to important issues in pediatric TBI is presented, and recent specific topics are also discussed. This review provides important updates on the pathophysiology, diagnosis, and age-appropriate acute management of pediatric TBI.
Patients with diffuse axonal injury (DAI) may initially present with prominent physical impairments, but their cognitive dysfunctions are more persistent and are attributable to later unemployment. In this study, we analyzed how the findings of early and delayed neuropsychological assessments correlated with employment outcome of patients with DAI. A total of 56 patients with DAI without motor or visual dysfunction were included in this study. The neuropsychological battery consisted of the Wechsler Adult Intelligent Scale - Revised (WAIS-R), Wechsler Memory Scale - Revised (WMS-R), Trail Making Test (TMT), Wisconsin Card Sorting Test (WCST), and Word Fluency Test (WFT). This battery of tests was administered twice in early stage after injury and in later stage. The results of all of the neuropsychological tests improved significantly (P <0.001) between the early and later assessments. All scores other than TMT part A and B improved to the normal range (Z-score ≥ 2). The patient characteristics (age, gender, initial Glasgow Coma Scale, and duration of posttraumatic amnesia) had no relationship to the outcome. The results of TMT part B, however, were significantly correlated with employment outcome in both the early and later assessments (P = 0.01, 0.04). Given that TMT evaluates visual attention, we surmise that a lack of attention may be the core symptom of the cognitive deficit and cause the re-employment failure in patients with DAI. TMT part B in both early and later assessments has the potential to accurately predict chronic functional outcome.
Ethical issues in the field of pediatric neurosurgery, including prenatal diagnosis, palliative care for children with an intractable serious disease, and medical neglect, are discussed. An important role of medicine is to offer every possible treatment to a patient. However, it also is the responsibility of medicine to be conscious of its limitations, and to help parents love and respect a child who suffers from an incurable disease. When dealing with cases of medical neglect and palliative care for an incurable disease, it is critical to diagnose the child’s condition accurately and evaluate the outcome. However, to treat or not to treat also depends on the medical resources and social-economic status of the community, the parents’ religion and philosophy, the policies of the institutions involved, and the limits of medical science. Moral dilemmas will continue to be addressed as medical progress yields treatments for untreatable diseases in the future.