Multicenter, Open-Label, Randomized Controlled Trial of Warfarin and Edoxaban Tosilate Hydrate for the Treatment of Deep Vein Thrombosis in Persons with Severe Motor Intellectual Disabilities.

Sudden death in patients with severe motor and intellectual disabilities (SMID) is sometimes caused in part by pulmonary thromboembolism (PTE), and deep venous thrombosis (DVT) has drawn attention as a possible embolic source. Warfarin, which is a conventional therapeutic agent, is not easy to control appropriately, and daily management can be especially difficult in SMID patients. On the other hand, edoxaban tosilate hydrate, which has been newly approved for insurance coverage for the treatment of DVT, is not listed in the Guidelines for the Diagnosis, Treatment and Prevention of Pulmonary Thromboembolism and Deep Vein Thrombosis (DVT-PTE guidelines). The aim of this study is to evaluate the efficacy and safety of anticoagulation therapy (warfarin vs. edoxaban) in DVT treatment in SMID patients by means of an open-label, randomized controlled trial. The primary endpoint is the incidence of hemorrhagic events during 12 months of follow up.

Anti-epileptics alter hypothyroidism of patients with severe motor and intellectual disabilities.

Objective: Anti-epileptic drugs, such as carbamazepine (CBZ) or phenytoin, may induce hypothyroidism in epilepsy patients. We assessed thyroid function of chronic patients with severe motor and intellectual disabilities (SMID) in our hospital. Methods: We examined thyroid-stimulating hormone (TSH), free thyroxine (fT4), and free thyronine (fT3) in 73 patients with SMID (47 men and 26 women, average age 48.4 years, range 30-68 years) without thyroid hormone supplement therapy. We determined the relationship between the thyroid function of patients taking the anti-epileptic drugs CBZ, valproate (VPA), and phenobarbital, other medications including anti-psychotic drugs, and treatments without anti-epileptic or anti-psychotic drugs. Results: TSH levels were not significantly different between the groups taking CBZ (CBZ+med), other anti-epileptic drugs or anti-psychotic drugs (CBZ-med), and only medications without anti-epileptic or anti-psychotic drugs (Non-med). The CBZ+med group had significantly lower fT4 levels than the CBZ-med or Non-med groups. There was a negative correlation between thyroid function level and the phenobarbital groups. TSH levels of the VPA+med group were significantly higher than VPA-med and Non-med group; fT3 and fT4 levels were not significantly different. Conclusions: Our results indicate that hypothyroidism may be present in patients with SMID taking anti-epileptic drugs. This suggests it is important to regularly measure thyroid function in patients with SMID taking anti-epileptic drugs, especially CBZ.

Ulcers on the epiglottis caused by a nasogastric tube in three adults with severe motor and intellectual disabilities.

Nasogastric tube feeding is a common method of parenteral nutrition. We observed ulcers on the epiglottis caused by a nasogastric tube in three adults with severe motor and intellectual disabilities (SMID) during examination with a laryngeal fiberscope while swallowing. These ulcers were healed by changing the method of inserting the nasogastric tube. The patients were three men aged 25, 39, and 55 years. The muscle tone of the whole body was increased in all of the patients. Two patients had severe scoliosis, and the other patient had lordosis in the thoracic vertebrae and had received laryngo-tracheal diversion. All of the patients received intermittent or continuous respiratory care. The pharynx of the patients with severe scoliosis became thinner and the feeding tubes ran obliquely. The feeding tube in the patient who received laryngo-tracheal diversion entered the cut and closed trachea through the glottis. Ulcers were observed on the laryngeal side of the epiglottis in all of the patients. The ulcers were healed by preventing feeding tubes from running obliquely or by using the naso-gastric tube made of different materials in the patients with severe scoliosis. In the patient who received laryngo-tracheal diversion, we succeeded in avoiding the glottis by keeping his face forward while inserting the feeding tube. Then feeding tubes were changed with guidewires, and the ulcers were healed. When using nasogastric tube feeding for persons with SMID with a large increase in muscle tone and/or with severe scoliosis, adopting a method of inserting feeding tubes that avoids damaging the epiglottis with a laryngeal fiberscope is required.

A case of megalencephalic leukoencephalopathy with subcortical cysts (van der Knaap disease): molecular genetic study.

Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is an autosomal recessive disorder characterized by macrocephaly, deterioration of motor function with ataxia, spasticity and mental decline. It has been revealed that the mutations in the gene, KIAA0027, were responsible for MLC and the gene was renamed subsequently 'MLC1'. A 41-year-old Japanese male with MLC, in whom a homozygous missense mutation, TCG to TTG at codon 93 resulting in S93L, was detected in the MLC1 gene, was described. MRI revealed marked cerebral atrophy and enlargement of the ventricular system. The subject's motor function had severely deteriorated, while his cognitive function had maintained at the level of a 2-year-old for the past 10 years. The mutation in the MLC1 gene of the patient is considered to be a common mutation responsible for MLC in Japanese patients because the same mutation had been detected in two other Japanese patients with MLC.

[Mortality patterns of non-institutionalized severely retarded children in Tokyo--the third report 1999-2001].

We investigated mortality patterns of severely retarded children who were cared at their homes in Tokyo ten years after our first report. During the past two and a half years (from April 1999 to September 2001), we identified 41 fatal cases. The annual case fatality rate (the mortality rate among the investigated children) was 8.2@1000 in all the school-attending children and was 10.1@1000 in children with severe motor and intellectual disabilities. The rate was less than half of that in our past report and seemed to the lowest among those in several studies. Aggravation of basal disorders, severe respiratory infections and/or sepsis, and unexplained sudden death accounted for most of the death. We conclude that advance of medical service and the propagated medical education of teachers working for special schools play an important role to reduce the mortality in severely retarded children.