Over the last three decades, many disease-responsible genes have been identified due to advancement of technologies in molecular biology. Methodologies to identify disease-responsible genes have been changed according to the history. Although large subject numbers were needed previously, valuable data derived from only one rare patient have led to identify some disease-responsible genes. Recently launched next-generation sequencers have heralded the new personal genome era. We should know that we may be able to identify some disease-responsible genes by the investigation of only one patient who we meet at the bed side.

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  We investigated the clinical course of 20 children (persons) with severe motor and intellectual disabilities (SMID) who were treated with noninvasive positive pressure ventilation (NPPV) for respiratory insufficiency. NPPV was effective in 10 of 11 patients treated for acute respiratory failure, and in 7 of 9 patients treated for chronic respiratory failure. Twelve patients were treated with NPPV for more than one year. There were no complications associated with NPPV in any of the patients. NPPV improved ventilation impairment soon after ventilation was started, and avoided the need for the endtracheal intubation by adjusting airway management and the choice of mask in all but one of the patients with acute respiratory failure. NPPV in combination with wearing a chin strap was highly effective in patients with open state or upper airway obstruction. Five patients were successfully weaned off the ventilator soon after recovery from acute respiratory failure using NPPV, whereas 5 patients who continued NPPV during the chronic phase after recovery did not experience recurrent episodes of acute respiratory failure. We conclude that NPPV may be an effective treatment for SMID with respiratory insufficiency.

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  Mothers of 18 children with attention deficit/hyperactivity disorders (AD/HD) and 6 with pervasive developmental disorders (PDD) underwent a parent training (PT) program. After the program, the Beck Depression Inventory-II (BDI-II) score, which indicates parenting stress, significantly decreased from 15 to 8 (p=0.036). A total of 22 mothers had increased parenting self-esteem, and better parent-child relationships were noted in these cases. An analysis of children's behavior by using Achenbach's Child Behavior Checklist showed that introversion tendency, physical failure, aggressive behavior, and extroversion score improved significantly after PT (p<0.05). After PT, out-of-control behaviors improved in 19 children and continued in 5. We conclude that PT for mothers of children with AD/HD and/or high-functioning PDD is effective in improving both the parenting skills of mothers and adaptive behaviors of children.

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  We reported 19 cases of school-aged children. They were initially judged to have learning difficulty or school maladaptation because of attention deficits, hyperactive behaviors or poor school performance, followed by the diagnosis such as degenerative or metabolic neurological diseases. The patients consisted of 4 cases of adrenoleukodystrophy, 5 cases of dentatorubral-pallidoluysian atrophy, 3 cases of Sanfilippo syndrome, 3 cases of subacute sclerosing panencephalitis, and each one case of juvenile Gaucher disease, juvenile Huntington disease, juvenile metachromatic leukodystrophy and Leigh disease.
  They had markedly poor school performance, and/or abnormal behaviors, followed by seizures, character disorders or psychomotor regression. The diagnostic clues included brain CT scan and/or MRI, peculiar facial appearance and notable family histories.
  When the children were indicated to have learning difficulty or maladjustment to school life, we should make deliberate differential diagnoses before concluding that they have a learning disorder and/or attention-deficit/hyperactivity disorder. Instead they should be recommended to visit child neurologists, when they present with any problems as aforesaid.

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  The effects of topiramate (TPM) were evaluated in 51 patients with intractable epilepsy. Callosotomy and hemispherotomy were performed in 16 patients and one patient before the administration of TPM, respectively. The 50% responder rate (50%RR) was recorded in 39% of the total patient population and in 58% of patients with symptomatic location-related epilepsy (SLE). TPM was most effective for frontal lobe epilepsy (FLE), and the 50%RR was recorded in 88% of those patients.
  TPM (50%RR) was more effective in secondary generalized seizures (in 75%) and complex partial seizures (in 67%) in comparison to that of tonic-clonic seizures (in 44%) and drop attacks (in 29%).
  Seventy-one percent of the patients with atypical absence seizures increased seizure frequency.
  The 50%RR was recorded in 22% of the patients who underwent epilepsy surgery, and 29% of those patients also showed seizure aggravation due to TPM. These results suggest the efficacy of TPM for intractable epilepsy.

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  Fifty-eight patients who visited the emergency room of our center with febrile convulsions and impaired consciousness, and underwent paperless electroencephalography soon after arrival. They consisted of 25 male and 33 female children, ranging in age from 5 months to 15 years and 4 months, with a mean age of 4 years and 10 months. The final diagnoses were poor responsiveness associated with fever and febrile delirium in 5 patients, febrile convulsions in 26, encephalitis/encephalopathy in 24, convulsions associated with mild gastroenteritis in 2, and aseptic meningitis in 1. The appearance of spindle wave within 24 hours after admission was considered to be a favorable prognostic factor, whereas generalized high-amplitude delta waves without fast-wave components and dysrhythmic flat basic waves were considered poor prognostic factors. We conclude that bed-side paperless electroencephalography is useful for the evaluation of changes in the brain function and course of treatment.

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  We conducted a questionnaire survey to investigate the situation of transitional medicine for epilepsy. Among the epilepsy patients cared by pediatric neurologists, 27% were adult patients including some elderly epilepsy patients. Seventy-six percent of the pediatric neurologists felt some difficulties in providing care for adult epilepsy. The main issues were psychiatric/psychological co-morbidity, medical co-morbidity, and a lack of in-patient facilities in the vicinity. This survey demonstrated that the lack of the transitional medicine for epilepsy in Japan is a profound problem, and the factors that hamper transfer of epilepsy patients to adult specialties should be resolved. To solve this problem, it is imperative that the Japanese Society of Child Neurology and Japan Epilepsy Society conduct collaborative activities with three relevant societies; Societas Neurologica Japonica, the Japanese Society of Psychiatry and Neurology, and the Japan Neurosurgical Society.

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  Treatment periods for bacterial meningitis are often very long, and often this prolonged treatment is based on the judgment of its effectiveness by the degree of enhancement on brain magnetic resonance imaging (MRI). In this study, we analyzed the contrast MRI in the acute and recovery phases of bacterial meningitis in twelve patients, and graded the contrast level of the subdural space and subarachnoid space separately. While the contrast level of the subarachnoid space increased with time in 4 cases, that of the subdural space increased in 10 cases, and 9 of them revealed a good prognosis without continuation of the treatment. These findings indicate that increased contrast level of the subdural space is common in the recovery phase of bacterial meningitis, and that repetitive MRI investigation is not valuable to determine the duration of treatment.

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  The current study sought to develop a new behavioral analysis methods to evaluate the effects of social skills training (SST). SST is known to be an effective method to improve the social skills of children with behavioral problems. However, current evaluation methods involve behavioral rating scales that are heavily dependent on evaluators' particular experiences they have had. To quantitatively examine the behavioral effects of SST, we examined subjects' head-movements related to social behavior, using a two-dimensional motion capture system (Kissei Comtec, Japan).
  Four children (three male, one female, 7-8 years of age) with pervasive developmental disorder (PDD) or attention deficit/hyperactivity disorder (AD/HD) participated in 16 sessions of SST. Before and after SST, head-coordinates on a two-dimensional plane were calculated using their behavior during a pair task, measured by four digital cameras.
  After SST, the number of communication behaviors was increased compared to before SST. In addition, children looked longer at another child within 30 degrees of the central visual field. Time-series analysis of the visual field during the detection of another child revealed significant auto-correlation from about -1.12 second. before to the beginning of communication behavior (p<0.05).
  The results suggested that our method can provide a quantitative index of characteristics related to skilled social behaviors. We conclude that a two-dimensional motion capture system would be useful for visualization of the interventional effects of SST, which would supplement assessments by the conventional observational strategies.

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  Objective: Severely handicapped children and adolescents have reduced bone mineral density and high prevalence of pathological fractures. Bone quantitative ultrasonography (QUS) is a radiation-free method for assessing bone density. It is portable and easy to use in subjects with severe bodily deformities.
  Methods: We evaluated 166 students (age 6-20 years) at a school for disabled children for bone mineral density using the osteo-sono-assessment index (OSI) calculated by measuring the velocity of ultrasound waves, the speed of sound (SOS) and the transmission index (TI), at the calcaneus. All examinations were performed using an AOS-100 analyzer (ALOKA Ltd., Tokyo, Japan). The Gross Motor Function Classification System (GMFCS) for cerebral palsy was also applied. We assessed OSI for dietary texture modifications and methods of feeding.
  Results: Those with pathological fractures tended to have lower OSI than other students. Such fractures were individually unrelated to age, sex and GMFCS. OSI was significantly higher at GMFCS level I than level II. OSI in levels I to III was equally significantly higher than that in levels IV and V. As to feeding methods, the tube feeding group tended to have lower OSI than the oral ingestion group. In the oral ingestion group, those receiving a regular diet had significantly higher OSI than the mixed-minced diet group.
  However, students with a gastrostomy tended to have higher OSI than those receiving gastro-nasal tube feeding.
  Conclusions: Gross motor function (applied GMFCS) is a major factor affecting bone mineral density. Tube feeding reduces bone mineral density. However, forced oral intake may also reduce it. In the tube feeding group, a modified diet of appropriate texture delivered via gastrostomy may be the key to improving bone mineral density.

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[in Japanese]

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