Masahiro Ishii

Background: Chromosome 5p partial monosomy (5p-syndrome) and chromosome 6p partial trisomy are chromosomal abnormalities that result in a variety of symptoms, but liver dysfunction is not normally one of them. Alagille syndrome (OMIM #118450) is a multisystem disorder that is defined clinically by hepatic bile duct paucity and cholestasis, in association with cardiac, skeletal, and ophthalmologic manifestations, and characteristic facial features. Alagille syndrome is caused by mutations in JAG1 on chromosome 20 or NOTCH2 on chromosome 1. Here, we report a preterm infant with karyotype 46,XX,der(5)t(5,6)(p15.2;p22.3) and hepatic dysfunction, who was diagnosed as having incomplete Alagille syndrome. Case presentation: The Japanese infant was diagnosed based on the cardiac abnormalities, ocular abnormalities, characteristic facial features, and liver pathological findings. Analysis of the JAG1 and NOTCH sequences failed to detect any mutations in these genes. Conclusions: These results suggest that, besides the genes that are known to be responsible for Alagille syndrome, other genetic mutations also may cause Alagille syndrome.

A seven year old patient with intractable epilepsy was admitted to our hospital. We used intravenous (IV) antiepileptic drug (AED) regimen to optimize the oral AEDs by adding newer AEDs, which have been reported to be beneficial when compared to older AEDs in controlling seizures. The patient was diagnosed with myoclonic, absence, astatic and tonic seizures. He was already on six oral AEDs, and we speculated that his seizures were intractable as he was on AED polytherapy. Therefore we substituted with newer AEDs and simultaneously treated with an IV AED as a base therapy (AED adjustment). The patient’s EEG was exacerbated when slow infusion Midazolam (MDL) at 0.1 mg/kg/dose and Phenobarbital at 10 mg/kg/dose was used. Fosphenytoin sodium hydrate (fos-PHT) was the only IV AED which improved the patient’s EEG. He had no seizures with IV fos-PHT at 10 mg/kg/day. We continued with treatment with Sodium valproate and stopped other five oral AEDs and did not notice any withdrawal effects or seizure exacerbation. Slow infusion of MDL (0.1 mg/kg/dose) improved his EEG significantly in a week, so we decided to stop fos-PHT and continue IV MDL 0.1 mg/kg/hr. Later, we gradually decreased the dose of MDL and choose oral AEDs in accordance with his seizure type. This reduced his oral AEDs to three. This case suggests that: 1) use of IV AED as a base therapy, can adjust patients’ AED treatment safely in a short period; and 2) In this particular case, newer AEDs was ineffective when administered along with AED polytherapy. Reducing the number oral AEDs administered to patients is a crucial goal when reassessing their oral AED regimen.

It is reported that 0.4 to 0.8% of the world’s population suffers from epilepsy. About 30% of epileptic patients are intractable. Controlling their seizures is very important for society because many patients can participate in gainful employment. In this case study we report how we reduce and/or change the oral antiepileptic drugs (AEDs) taken (AED adjustment) by administering intravenous (IV) AED for an intractable epileptic patient. The patient was introduced to our hospital when she was 17 years old. She was born as a premature baby and had been suffering from partial seizures since she was 1 year old. We adjusted her oral AEDs in order to add newer AEDs, but the drugs did not work effectively. Thus, we hospitalized her in order to use continuous intravenous Midazolam (MDL) 0.1mg/kg/hr while we adjusted her AEDs. We were able to stop administering four out of five kinds of AEDs that the patient was taking simultaneously, without exacerbating her seizures. This case suggests that: 1) when intractable epileptic patients are taking a large number of oral AEDs, newer, additional AEDs cannot work effectively, and reducing the number of oral AEDs is crucial in adjusting their oral AEDs; and 2) IV AEDs enable a reduction in the number of oral AEDs in a short period of time without seizure exacerbation, thus facilitating safe adjustment of oral AEDs.

We present two patients with epileptic spasms without hypsarrhythmia (ESWoH) who were successfully treated with ACTH. One patient was an 18-month-old boy who had normal development for the first 16 months of his life. Thereafter, he experienced sudden flexion of the axial muscles, resulting in head nodings, or epileptic spasms (ES). EEG tracings showed generalized polyspikes that appeared frequently during sleep without associated hypsarrhythmia. We were thus able to diagnose him with ESWoH and treated him with ACTH, which resolved his seizures. Another patient was a 7-year-old boy. At 18 months of age, the patient began to sufferdil from sudden ES. Anti-epileptic drugs were administered individually and in combination but were proved ineffective. Like the first case, this child's EEG tracing showed generalized polyspikes during sleep without associated hypsarrhythmia. We diagnosed him with ESWoH and treated him with ACTH. His ES disappeared soon after the initiation of treatment. These two cases demonstrate the difficulty of treating ESWoH only with standard anti-epileptic drugs, we emphasize the importance of early treatment with ACTH.

We herein report a 3 year-old boy, who showed proximal muscle weakness and pain at the age of one and a-half years. When he visited our hospital at the age of 1 year and 11 months, he could hardly move by himself. He also had difficulty in swallowing and suffered from multiple dermal ulcers. His blood test showed slightly elevated muscle enzyme activity, and magnetic resonance imaging suggested severe inflammation of the muscles. Radiological examination proved hypoperistalsis of the esophagus. With additional skin and muscle biopsies, we diagnosed him with juvenile dermatomyositis (JDM). Methyl-prednisolone pulse therapy was not effective enough, thus oral methotrexate, cyclosporine A and monthly cyclophosphamide pulse therapy were added. After the fourth cyclophosphamide pulse therapy, his muscular strength was restored, and the ulcers healed dramatically. Due to scarcity of severe cases, neither standardized classification nor grading system for severity in JDM has ever been established, which perplexes physicians in finding the best therapeutic strategy. Further investigation, experience and efforts are necessary to standardize an evaluating system and therapeutic strategy against JDM.

We here report on a male infant with Ohtahara syndrome. Tonic spasms in series appeared in an one-month-old baby, with his EEG showing a typical suppression burst pattern. We attempted these therapies in the following order; high-dose pyridoxal phosphate; anti-epileptic drugs; sodium valproate, phenobarbital, clonazepam and clobazam in various doses and combination; ACTH; TRH; and gamma-globulin. These did not, however, prove effective enough. Then we tried the ketogenic diet and brought his seizures under control. Therefore, we recommend that doctors who treat Ohtahara syndrome consider using the ketogenic diet earlier in the treatment regimen if the patient does not seem to be responding to conventional drug therapies.