Niemann-Pick type C (NPC) disease is an autosomal recessive neurodegenerative disorder which is caused in 95% by a mutation in the NPC1 gene on chromosome 18 or by NPC2 mutation, encoding for 2 different lysosomal lipid transport proteins. The impaired protein function leads to systemic intralysosomal accumulation of free cholesterol and shingolipids particularly in the CNS.
  In Japan, currently 34 living NPC patients are known as of December 2015. Considering the prevalence of the disease in the Western countries, the real number of NPC patients is most likely to be five-folds higher. For NPC, treatment methods are established and an approved disease-specific medications are available. It is important that patients early in their disease are referred to expert centers, in order to ensure timely initiation of treatment and to delay the progression of neurological symptoms as a goal.

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[in Japanese]

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  Objective: Self-injurious behavior (SIB) is a common problem in individuals with intellectual disabilities, yet its clinical management remains to be established. We aimed to clarify the background factors and profiles of SIB in mentally and physically handicapped subjects and subsequently examined the efficacy of treatments attempted in our practice in order to achieve a better understanding of SIB and appropriate interventions in these populations. Methods: We surveyed 92 mentally handicapped subjects with SIB (including 25 females and 67 males, most of whom also had physical disabilities) as outpatients or inpatients of our institution using a retrospective questionnaire completed by the corresponding doctors. Results: Regarding psychobehavioral complications, impulsive mood swings (such as sudden rage) were more frequent than other behaviors. As to probable triggers of SIB, the patient’s physical condition (17 cases) and noise or the temperature of the surrounding environment (38 cases) were identified. A total of 81 of 92 patients were given a prescription for SIB. Risperidone was the most commonly prescribed drug (75 cases), found to be effective in 38 (50.6%) cases, whereas phenothiazine antipsychotics were often more effective in patients with profound SIB. SSRIs (selective serotonin reuptake inhibitors) were applied in 20 cases, being effective in only five (25%) patients and discontinued in 11 (55%) patients due to the onset of several side effects, including overexcitement. As an additional agent for mood control, the antiepileptic topiramate was effective in 10 (76.9%) of 13 cases. Aside from medication, equipment for elbow extension was beneficial in some of the patients with profound SIB. Conclusions: Pharmacological intervention is sometimes beneficial, albeit only partly. Clinicians must therefore also consider triggers and factors in the surrounding environment for the development of SIB in mentally handicapped individuals.

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  Objective: There have been many reports on the effects of early rehabilitation in children with Down syndrome, which have demonstrated that early intervention improves motor skill acquisition and prevents a shuffling gait in these children. With regard to the mental development and mental health of these children, they are known to be friendly and social but some experience difficulties with nursing. Recently there have been a few reports on comorbidities of developmental disorders in Down syndrome. In the present research we studied both the motor and mental developments in children with Down syndrome, paying special attention to the shuffling gait and the comorbidities of developmental disorder. Methods: Clinical records of 121children with Down syndrome (age, 1-11 years ; mean age, 3.8 years), who visited the Yokohama rehabilitation center, were investigated. Results: Despite early intervention, we found that 14 patients (11.9%) exhibited a shuffling gait. Concerning the comorbidities of the psychiatric developmental disorder, 21 patients (17.4%) had autism spectrum disorder (ASD) -like characteristic. The children with a shuffling gait appeared slow with regard to motor developmental milestones. They also had ASD-like characteristics. Conclusions: Children with Down syndrome needed early rehabilitation not only for its motor skill effects but also for mental support. In spite of early intervention, those with a shuffling gait needed special care owing to the comorbidities such as ASD-like characteristics. More research is needed to establish the prognosis of Down syndrome.

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  We report the case of a 4-year-old girl who presented with paroxysmal sympathetic hyperactivity (PSH), after developing severe hypoxic-ischemic-encephalopathy because of cardiopulmonary arrest. She showed dramatic paroxysmal sympathetic activity with dystonia. She was treated with wide variety of medications against PSH, which were found to be effective in previous studies. Among them, morphine, bromocriptine, propranolol, and clonidine were effective in reducing the frequency of her attacks while gabapentin, baclofen, dantrolene, and benzodiazepine were ineffective. Though the paroxysms decreased markedly after the treatment, they could not be completely controlled beyond 500 days. Following the treatment, levels of plasma catecholamines and their urinary metabolites decreased to normal during inter-paroxysms. However, once a paroxysm had recurred, these levels were again very high. This case study is considered significant for two reasons. One is that PSH among children have been rarely reported, and the other is that this case of prolonged PSH delineated the transition of plasma catecholamines during the treatment. The excitatory : inhibitory ratio (EIR) model proposed by Baguley was considered while discussing drug sensitivity in this case. Accumulation of similar case studies will help establish more effective treatment strategies and elucidate the pathophysiology of PSH.

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  A 3-month-old girl exhibited asymmetric abnormal eye movement and unilateral dystonic posture intermittently after the first few days of life. Unilateral ocular deviation or nystagmus were the main signs of abnormal eye movements. She was suspected to have alternating hemiplegia of childhood (AHC) despite the absence of apparent alternating hemiplegic episodes. Gene analysis revealed a de-novo missense mutation (Asp801Asn) of ATP1A3. AHC is a rare neurodevelopmental disorder characterized by recurrent transient attacks of hemiplegia affecting the unilateral or bilateral side of the body ; in most cases, these attacks begin in the first 6 months of life. Initial symptoms of AHC are not alternating hemiplegic episodes, but rather asymmetric abnormal eye movement, dystonic posture, or seizures. It is difficult to diagnose AHC early because no specific findings are observed in the diagnostic laboratory or neuroradiological examinations. Early diagnosis is important because flunarizine may have a protective effect on the severe motor deterioration associated with AHC. Asymmetric abnormal eye movement could be an important clinical symptom for the diagnosis of AHC in early infancy.

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