Atsushi Araki

Successful control with bromide of two patients with malignant migrating partial seizures in infancy

A 3-month-old male and a 4-month-old female infant with intractable seizures were diagnosed as having malignant migrating partial seizures in infancy (MMPSI) with developmental arrest on the basis of characteristics of symptoms, clinical courses and EEGs. We treated these two patients with potassium bromide (80 mg/kg) after conventional antiepileptic drugs failed to adequately control the seizures. The potassium bromide therapy resulted in complete control of seizures in one patient, and more than 95% reduction in seizure frequency in the other.

Genotype–phenotype correlations in alternating hemiplegia of childhood

Objective: Clinical severity of alternating hemiplegia of childhood (AHC) is extremely variable. To investigate genotype–phenotype correlations in AHC, we analyzed the clinical information and ATP1A3 mutations in patients with AHC. Methods: Thirty-five Japanese patients who were clinically diagnosed with AHC participated in this study. ATP1A3 mutations were analyzed using Sanger sequencing. Detailed clinical information was collected from family members of patients with AHC and clinicians responsible for their care. Results: Gene analysis revealed 33 patients with de novo heterozygous missense mutations of ATP1A3: Glu815Lys in 12 cases (36%), Asp801Asn in 10 cases (30%), and other missense mutations in 11 cases. Clinical information was compared among the Glu815Lys, Asp801Asn, and other mutation groups. Statistical analysis revealed significant differences in the history of neonatal onset, gross motor level, status epilepticus, and respiratory paralysis in the Glu815Lys group compared with the other groups. In addition, 8 patients who did not receive flunarizine had severe motor deteriorations. Conclusions: The Glu815Lys genotype appears to be associated with the most severe AHC phenotype. Although AHC is not generally seen as a progressive disorder, it should be considered a disorder that deteriorates abruptly or in a stepwise fashion, particularly in patients with the Glu815Lys mutation.

When do brain abnormalities in cerebral palsy occur? An MRI study

The authors used MRI to analyse retrospectively the brain images of patients with cerebral palsy (CP) to evaluate its the role in the assessment of brain abnormalities and injury, and the relationship of pre‐, peri‐ and postnatal events to CP. 70 patients with CP aged two to 16 years who underwent MRI were divided into four groups: group 1 (26 patients) comprised subjects whose CP was considered to have been caused by neuronal migration disorders in the embryonal stage; group 2 (30 patients) contained subjects whose cause was vascular disorders; in group 3 patients (five) the cause was intra‐uterine infection; and CP clearly attributable to birth asphyxia (group 4) was noted in only nine patients. The results indicate that CP of term infants is often the result of prenatal factors, and their MRI findings indicated migration and cerebral infarction. Brain MRI is an essential examination in identifying the factors causing brain damage in CP.

Hepatotoxicity in Rat Following Administration of Valproic Acid: Effect of L-Carnitine Supplementation

Summary: The effect of prolonged administration (7 days) of valproate (VPA, 500 mg/kg/day), or VPA (500 mglkglday) with L‐carnitine (200 mg/kg/day) on blood carnitine levels and the appearance of liver mitochondria were assessed in the rat. VPA‐treated rats showed hypo‐ carnitinemia and enlarged mitochondria when compared with saline‐injected control rats. In rats treated with bothVPA and L‐carnitine, serum and liver carnitine levels were increased by the L‐carnitine supplement and the liver mitochondria were not enlarged. L‐Carnitine supplement in VPA‐medicated patients seems to prevent hepatotoxicity, especially mitochondrial dysfunction.

Carnitine Metabolism in Valproate-Treated Rats: The Effect of L-Carnitine Supplementation

ABSTRACT. The effect of the administration for 7 days of valproate (500 mg/kg/day) or valproate (500 mg/kg/day) plus L-carnitine (200 mg/kg/day) on carnitine concentrations in serum, red blood cells, muscle, liver, and urine was evaluated. In the serum and muscle of the valproic acid (VPA) group, free carnitine levels decreased, while acylcarnitine levels and acyl/free ratio increased, when compared to those of the control. When L-carnitine was given to the VPA group, the free carnitine levels increased in the serum, muscle, and liver, and the acyl/free ratio decreased in all tissues when compared to those of the VPA group. The mean of free carnitine level in urine of the VPA group was not different but acylcarnitine increased when compared to values of controls, and after the supplementation with L-carnitine the acylcarnitine (from day 4 to 7) levels were decreased compared to the VPA group. The serum β- OH-butyrate level in the VPA group was decreased when compared to those of controls and VPA plus L-carnitine groups. These results indicate that L-carnitine supplementation protects against the alteration in carnitine metabolism induced by the administration of VPA.

The effects of stimulus rates on the amplitude of median nerve somatosensory evoked potentials: the developmental change

We examined the effects of stimulus rates on the somatosensory evoked potential (SEP) amplitudes following median nerve stimulation at the wrist in 42 children. We divided these subjects into five groups according to their age (0-6 months, 7-12 months, 1-3 years, 4-6 years and more than 7 years) and measured the peak-to-peak amplitude of every component (N9, P10, N11, P13/14, N18, N20, P23, N30) at stimulus rates of 1.0, 3.5 and 5.5 Hz. From N9 to N18, there was no significant change in amplitude nor latency with stimulus rate change in all groups. The amplitude attenuation was found at the N20 and N30 peaks in the young group (0 months to 3 years) and at P23 in all groups with an increasing stimulus rate. The attenuation rate of P23 amplitude was influenced by the age of subjects, being greater in younger groups and greatest in the youngest group (0-6 months). The differences of amplitude attenuation rate between this group and the rest were statistically significant. The results of this study indicate that the amplitudes of the cortical components of SEP in children are greatly influenced by the stimulus rate. Thus when we discuss the amplitude of cortical waves in childhood, we should also pay attention to the stimulus rates.

Usefulness of diffusion-weighted MRI in human herpesvirus-6 encephalitis

We report a patient with human herpesvirus‐6 (HHV‐6) encephalitis diagnosed by diffusion‐weighted magnetic resonance imaging (DW‐MRI). A previously healthy 10‐month‐old girl developed acute encephalopathy. HHV‐6 DNA was detected in her cerebrospinal fluid during the acute phase of the disease by polymerase chain reaction. The patient demonstrated cortical diffusion abnormalities in affected brain parenchyma, partially as the initial or most sensitive sign of encephalitis that could be detected not by conventional MRI but by DW‐MRI. Serial imaging showed that the diffusion abnormality DW‐MRI returned to normal after 45 days.

Magnetic resonance imaging of brain lesions of a patient with hemolytic uremic syndrome following Escherichia coli O157 infection

infection has been shown to be associated with hemolytic uremic syndrome (HUS)1 and the central nervous system (CNS) manifestations of HUS are considered to be important predictive factors of HUS mortality in children.2 In the summer of 1996, more than 6000 children in Sakai City, Osaka, Japan, became ill with VTEC and several of them showed CNS symptoms associated with HUS. The etiology of CNS abnormalities observed in HUS remains to be determined. The purpose of the present article is to describe the treatment of a female patient during the above outbreak and to attempt to clarify the pathogenesis of CNS manifestations with HUS based on magnetic resonance imaging (MRI) findings.

Alterations of Urinary Acetylcarnitine in Valproate-Treated Rats: The Effect of L-Carnitine Supplementation

Urinary excretion of acetylcarnitine was measured by high-performance liquid chromatography in two experimental groups of valproate-treated rats. In the urine of mature rats weighing 180 to 200 g treated with valproate (500 mg/kg/day), acetylcarnitine levels were higher than those in controls on days 4 and 7, while L-carnitine-supplemented rats showed lower levels than the valproate group. The valproate-treated rats showed an increased acetylcarnitine/acylcarnitine ratio on and after day 4, while the L-carnitine-supplemented rats showed no significant change compared to the controls on any days. In the urine of immature rats weighing 80 to 90 g treated with valproate (50 mg/kg/day), acetylcarnitine levels were increased after the 14th day of treatment. These results suggest that an increase in urinary acetylcarnitine occurs when small doses of valproate are administered for a longer time. We speculate that increased acetylcarnitine is not a product of β-oxidation in mitochondria, because L-carnitine supplementation decreases the acetylcarnitine levels. Although the mechanism of acetylcarnitine excretion during valproate administration is not clear, L-carnitine supplementation is effective in decreasing the level of urinary acetylcarnitine and keeping the acetylcarnitine/acylcarnitine ratio normal. (J Child Neurol 1992;7:404-407).

The effect of L-carnitine supplementation in 4 pentenoic acid treated rats

The effects of prolonged administration (7 days) of 4 pentenoic acid (4PA, 20 mg/kg/day) or 4PA (20 mg/kg/day) with L-carnitine (200 mg/kg/day) on carnitine metabolism and morphological changes of liver mitochondria were assessed in rats. 4PA-treated rats showed hyperammonemia, decreased levels of blood glucose, free fatty acids and beta-OH-butyrate, and of free carnitine in serum, muscle and liver, increased excretion of acylcarnitine in urine, and enlarged mitochondria with microvesicular steatosis, when compared to saline-injected control rats, respectively. 4PA plus L-carnitine rats showed decreased levels of blood ammonia and increased levels of beta-OH-butyrate, compared to the 4PA group. On the other hand, the levels of free carnitine in serum and liver in rats treated with both 4PA and L-carnitine were increased, when compared to controls. The ratio of acylcarnitine to free carnitine excreted in urine in 4PA-treated rats was higher than that in either the control or 4PA plus L-carnitine group. The liver mitochondria in the 4PA plus L-carnitine group were the same as in the controls. The results suggested that the abnormal biochemical and morphological findings due to only 4PA may be relieved with L-carnitine supplementation.