The importance of nutritional management has recently been at the forefront of medicine. This also applies to the pediatric field, in which patients are often treated with special milk and enteral nutrient formulas. To meet this demand, various types of formula have been developed. However, some of these products lack sufficient levels of some necessary nutrients, and severe nutritional deficiencies have been reported in patients treated with these special milk and enteral formulas. Milk used to treat patients with inborn metabolic disorders, as well as those with milk allergies and ketogenic formulas, and some enteral nutrient formulas lack sufficient amounts of biotin, carnitine, selenium, and iodine. This suggests that special care to avoid a deficiency of nutrients must be taken when treating patients with special milk or enteral nutrient formulas.

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  Objective: Persons with severe motor and intellectual disabilities (SMID) caused by injury to the developing brain sometimes present generalized hypertonia in a specific position with extreme muscle overactivity persisting for most of the time during wakefulness. This “persistent generalized muscle contraction” is often associated with bad humor, sleep disturbance, hyperhidrosis, wasting, elevation of serum creatine kinase levels, regular daytime use of hypnotic or sedative medication, and the necessity to maintain the neck or hip in a flexed position manually. The aim of this study is to elucidate the clinical profile of this condition. Methods: We retrospectively examined the medical records and brain imaging data of 66 SMID patients in the state of persistent generalized muscle contraction. Results: Most patients could be classified into 2 major categories on the basis of clinical presentation and brain imaging : (A) those with premature birth and bilateral lesion of globus pallidus interna (kernicterus) (n=16), and (B) those with various widespread bilateral basal ganglia/thalamic and/or cerebral lesions such as hypoxia-ischemia, acute encephalopathy, malformation, etc (n=50). Group A assumed an asymmetrical tonic-neck-reflex-like position, torsion of the trunk, fluctuation of hypertonia, and better mental development. Three of them exhibited extreme hypertonia resembling status dystonicus. Group B often exhibited persistent and fixed retroflexion of the neck and trunk or opisthotonus. Drugs such as oral muscular relaxants were ineffective in both groups. Injection of botulinum toxin into the cervical and paravertebral muscles partially alleviated symptoms. Conclusions: Persistent generalized muscle contraction in SMID has at least two different types. Group A has characteristics of severe dystonic hypertonia that could lead to status dystonicus. Group B might have peculiar characteristics of muscle overactivity triggered by wakefulness or discomfort, which probably results from inability to achieve spontaneous muscle relaxation.

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  Objective: We investigated the clinical efficacy and pharmacokinetics of lamotrigine (LTG) as an add-on therapy in childhood-onset intractable epilepsy. Methods: We reviewed the charts of 28 outpatients who had received LTG as an add-on therapy. The data collected included epilepsy type, seizure frequency, concomitant anti-epileptic drugs, dosage of LTG and LTG serum levels. Furthermore, we reviewed the relationship between the LTG serum levels (μg/ml) and dosage of LTG (mg/kg/day), as well as the relationship between the LTG serum levels (μg/ml) and clinical efficacy in the following 2 groups: the valproate sodium (VPA) combination group and the non-VPA combination group. Results: A reduction of 50% or more in seizure frequency was observed in 10 patients. In addition, there was a high correlation between the LTG serum levels and the dosage of LTG in each group. In the VPA combination group, the average of LTG serum levels in patients with adequate therapeutic response (50% reduction in seizure frequency) was higher than that in patients without adequate therapeutic response. In the non-VPA combination group, the average LTG serum level in adequate response patients was lower than that in patients without adequate therapeutic response. However, the epilepsy types of adequate response patients differed in the two groups. Conclusions: The LTG serum level is predictable based on the dosage of LTG. It was judged that the effective blood concentration of LTG differed when used with VPA, although factors other than the combined use of VPA should have been taken into consideration also.

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  Objective: Currently, extended-release methylphenidate (MPH) and atomoxetine (ATX) are used for the medical treatment of AD/HD. The purpose of this study is to investigate the current state of these treatments from the viewpoint of the persistency rate of each drug. Methods: Of patients who had AD/HD or pervasive developmental disorder (PDD) associated with the symptoms of AD/HD, 460 cases who receiving MPH and 121 receiving ATX were investigated in terms of the diagnosis, the persistency rate, the persistency rate by the diagnostic name, reasons for discontinuation, and concomitant drugs as continual medications. Results: The cases who continued MPH accounted for 59.8% (275/460), and those who continued ATX accounted for 49.6% (60/121). There were 40 cases who received MPH and ATX concomitantly. The persistency rate of ATX among those who had PDD was low. Conclusions: The persistency rate of ATX was low because it was used for serious cases and MPH included the cases with proven effectiveness and discontinuation. There were also many cases requiring combination therapy. MPH had a high persistency rate for PDD, which did not necessarily mean that it was generally effective.

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  Objective: To examine indications for the early diagnosis of Menkes disease (MD). Methods: We compared clinical examination results of 3 neonate males with family histories of MD who were at risk of being affected (1 infant was affected and 2 were unaffected). Results: Kinky hair, a characteristic shown by MD patients, was observed just after birth in the affected infant; however, this characteristic was extremely mild and easy to miss. In the first month after birth, serum copper level declined over time in the affected infant, while it increased in the unaffected infants. Urine homovanillic acid/vanillylmandelic acid (HVA/VMA) ratio, which is typically high in MD patients, was observed to be 4.9-8.0 (cut-off, 4.0) in the affected infant. In the unaffected infants, the urine HVA/MVA ratio showed a high value of 11.0 during catecholamine administration, but this decreased to below the cut-off value when catecholamine was not administered. Conclusions: Variations in the serum copper level and urine HVA/VMA ratio over time were considered as useful indicators for the early diagnosis of MD.

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  A ten-month-old male infant fell onto the floor from a chair of 50 cm in height and hit his head on the day before hospitalization. He was admitted due to acute subdural hematoma, which was associated with arachnoid cyst. Head CT conducted on the 4th day confirmed that the hematoma had not enlarged. After discharge, enlargement of the hematoma was detected on MR imaging conducted on the 65th day after injury, followed by the diminution without surgical treatment. MR images were obtained on the 192nd day. In the case of head injury associated with arachnoid cyst, the risk of subdural hematoma as well as its ensuing enlargement in subacute or chronic phase needs to be considered.

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  Wernicke's encephalopathy (WE) is an acute neurological disease resulting from thiamine (vitamin B₁) deficiency. WE is often caused by an unbalanced diet or excessively strict diet therapy in pediatric cases. We experienced 2 cases of WE due to excessive intake of isotonic drink. Patient 1 was a 15-month-old boy. After frequent vomiting, he presented with mental status changes, ocular abnormalities, and truncal ataxia (the classic triad). Patient 2 was a 7-month-old boy. He was hospitalized because of status epilepticus. In both cases, the clinical symptoms improved immediately after the administration of vitamin B₁. However, mental retardation was observed as a neurological sequel in patient 2. Because many patients with WE present with vomiting at an early stage, we should take care not to confuse WE with gastroenterocolitis. In addition, it should be noted that some patients with WE present with seizure. Because these 2 cases resulted from an unbalanced diet, it is important to evaluate the patients' eating and drinking habits and advise their parents on proper nutrition. Since many people believe that isotonic drinks are very beneficial and consume them frequently, we should promote awareness that they can be harmful when consumed in excess.

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  MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) is the most representative subtype of mitochondrial diseases. Administration of L-arginine (L-Arg) or a precursor of nitric oxide (NO) has been proposed as a promising medication for MELAS because one of the pathophysiological mechanisms is supposedly a decreased capacity for NO-dependent vasodilation. We experienced a girl with MELAS and frequent stroke-like episodes who was treated with L-Arg infusion. We evaluated the efficacy of L-Arg infusion therapy based on whether her headache and nausea were disappeared and neurological symptoms were improved within 24 hours of L-Arg administration. L-Arg infusions were effective in all four episodes when the treatment was started within 4 hours of the onset of stroke-like episodes. On the other hand, the infusion was effective in only one out of five episodes when the medication was delayed by more than 4 hours after the onset. Furthermore, the early administration of L-Arg resulted in better outcomes regarding new lesions determined by brain MRI. Our data suggest that L-Arg infusion may be most effective when it is started within 4 hours of the onset of neurological symptoms in the acute phase of MELAS. The study of a large number of episodes in many patients will be needed to determine the critical time point of L-Arg administration after the onset of the acute phase of MELAS.

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[in Japanese]

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