Mitsuo Maehara

Mechanisms of T-type calcium channel blockade by zonisamide

We investigated the effects of zonisamide, a new antiepileptic drug, on voltage-dependent T-type calcium current (ICa) in cultured neuroblastoma cells of human origin (NB-I). Zonisamide reduced T-type ICa in a concentration-dependent manner without evoking any change in its inactivation kinetics or voltage dependence of action. The mean percent reduction was 38.3 +/- 5.8% at 50 microM. Further, zonisamide shifted the inactivation curve approximately 20 mV negative compared to the control. These resting blocking actions suggest that zonisamide shifts the channel population toward the inactivation state, allowing fewer channels to open during membrane depolarization. The blockade of T-type calcium channels by zonisamide could suppress an important component of inward current that underlies epileptiform cellular bursting, thereby inhibiting the spread of seizure activity.

Benign Infantile Epilepsy with Complex Partial Seizures

Benign infantile epilepsy with complex partial seizures is characterized by a high incidence of family history of benign childhood convulsions, normal development prior to onset, infantile onset, no underlying disorders, no neurological abnormalities, normal interictal EEGs, good response to treatment, and complete remission with normal developmental outcome. Seizures often occur in clusters, consisting of motion arrest, decreased responsiveness, staring or blank eyes mostly with simple automatisms, and mild convulsive movements associated with focal paroxysmal discharges, most frequently in the temporal area.

Antiepileptic drugs—calcium current interaction in cultured human neuroblastoma cells

The voltage-dependent calcium channel current (ICa) in the neuroblastoma cell line of human origin (NB-I) was studied by the whole-cell clamp recording. Three types of ICa were identified in NB-I cells. Our electrophysiological and pharmacological findings have suggested that these three types of ICa are consistent with the T-, N- and L-type ICa, respectively. Phenytoin (PHT) inhibited T-type ICa by 13.0% at a concentration of 5 microM, and L-type ICa by 6.3% at a concentration of 100 microM. At a concentration of 100 microM, carbamazepine (CBZ) inhibited T- and L-type ICa by 6.0% and 5.9%, respectively. At a concentration of 50 microM, sodium valproate (VPA) blocked T- and L-type ICa by 6.1% and 47.5%, respectively. At a concentration of 50 microM, zomisamide (ZNS) inhibited T- and L-type ICa by 38.3% and 41.9%, respectively. Na+ channel blockade has been reported to be responsible for the clinical efficacy of PHT or CBZ. Inhibition of T-type ICa by PHT may enhance the efficacy of its anticonvulsant action. CBZ had little effect on ICa. The anticonvulsant activity may be related to the blockade of T-type ICa in the case of VPA and ZNS.

Cytochrome c oxidase deficiency in menkes kinky hair disease

In a 4-year-old male with Menkes kinky hair disease (MKHD) treated with copper supplement therapy, reduced cytochrome a + a3 contents in liver was demonstrated to be 0.029 against 0.128 nmol/mg protein in the control. Cytochrome c oxidase activities in brain, liver, skeletal muscle, and heart were 47, 22, 54 and 59% of the control, respectively. The copper contents in brain and liver were decreased. In spite of increased serum levels of copper and ceruloplasmin, the decreased cytochrome c oxidase activities in various organs were not corrected by copper supplement therapy. A search for a therapeutic method which can normalize copper enzymes in brain and liver, would seem to be a prerequisite for the treatment of MKHD.

Moyamoya disease presenting with chorea

Three children with moyamoya disease are reported whose initial and predominant manifestations were choreic movements. Two of the patients presented with unsteady gait and the other with clumsiness. Choreic movements were recurrent and were often triggered by excitement, emotional tension, or crying. They occurred unilaterally or bilaterally and often alternated between the right and left. Moyamoya disease must be considered in the differential diagnosis of acquired chorea in children.

Hyperargininemia: Clinical course and treatment with sodium benzoate and phenylacetic acid

In a patient with hyperargininemia, oral administration of sodium benzoate or phenylacetic acid together with an essential amino acid mixture was used to prevent hyperammonemia and to decrease plasma and CSF concentrations of arginine. Sodium benzoate reduced the plasma ammonia levels, which was confirmed by the increase of urinary excretion of hippuric acid. Phenylacetic acid also controlled hyperammonemia, and EEG findings also improved. By these treatments, plasma and CSF concentrations of arginine showed a slight decrease, but were far above the normal range. There was no clinical improvement, and spasticity of the lower and upper extremities was progressive with mental deterioration.

Increment of α B-crystallin mRNA in the brain of patient with infantile type Alexander's disease

Abstract To estimate the expression level of α B-crystallin in the brain of infantile type Alexanders disease, the amounts of protein and mRNA of α B-crystallin were measured by enzyme immunoassay (EIA) and Northern blot analysis, respectively, in the brain of patient and controls, and in the tissues from glioblastoma and astrocytoma. The α B-crystallin protein in the brain of patient was remarkably increased as compared with those of controls. The amount of α B-crystallin mRNA of patient was increased about 7-fold compared to the mean value of the control group and higher than that of glioblastoma tissue. These data suggest that increment of α B-crystallin mRNA in astrocytes leads to the overexpression of this protein and may be one of the main causes of infantile type Alexanders disease.

Epileptic Nystagmus Associated with Typical Absence Seizures

Summary: A 10‐year‐old girl was reported who showed horizontal nystagmus in association with typical absence and 3‐cycles/s generalized, bisynchronous spike‐and‐wave discharges. In view of the general concept that epileptic nystagmus is a manifestation of partial seizures, the occurrence of such an association deserves documentation.

A simple fluorometric method for the determination of serum free carnitine

A new fluorometric method for the determination of serum free carnitine is described. The addition of carnitine to a system containing carnitine acetyltransferase (EC 2.3.1.7) and acetyl-CoA gives rise to the formation of CoA. The system is coupled to N-(p-(2-benzimidazolyl)-phenyl)-maleimide (BIPM). A fluorescent agent, CoA-BIPM, is produced proportionally to concentration of carnitine. By measuring the fluorescence intensity of BIPM, the carnitine content of serum can be determined. The coefficients of variation, within-run and between-run, of the method were 5.2 and 2.6%, respectively. Recovery of carnitine added to serum was 98-113%. Comparison with a colorimetric method showed a good correlation (r greater than 0.90). The method has sufficient sensitivity to measure concentrations as low as 10 mumol/l.

Magnetic Resonance Imaging in Complex Partial Seizures

Abstract: Magnetic resonance imaging (MRI) and computed tomography (CT) were performed on 45 patients with intractable complex partial seizures. MRI was performed with a super conducting whole‐body scanner operating at 0.5 tesla (T) and 1.5 T. In patients with temporal lobe epilepsy, 8 of 24 patients had abnormal CT, but 16 of 24 patients showed abnormal MRI. 1.5 T MRI detected more abnormality than 0.5 T MRI when CT was normal. In patients with frontal lobe epilepsy, 5 of 7 patients had normal CT and MRI. In 2 other patients, MRI demonstrated an arachnoid cyst and increased signal intensity area on the T2‐weighted images, which were not detected by CT. In patients with occipital lobe epilepsy, 5 of 6 patients show abnormal CT and MRI. In patients with tuberous sclerosis, MRI revealed some increased signal intensity areas on the T2‐weighted images in the occipital and temporal lobe, which were not detected by CT. Most surface EEG foci corresponded with the side of MRI abnormality. These data indicate that MRI is more informative than CT in complex partial seizures. MRI is the imaging technique of choice in the diagnosis of complex partial seizures.