Masao Kito

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.

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.

Severe myoclonic epilepsy in infancy: evolution of seizures

Changes in seizure type of severe myoclonic epilepsy (SME) in infancy were reviewed retrospectively in 14 patients (11 males and 3 females) who were followed-up to the age of 7 years or more. The observation period ranged from 5 to 16 years with a mean of 10 years. During the follow-up, three or four types of seizures were seen per patient, but the pattern of appearance and disappearance of each seizure type varied considerably among the patients. Tonic-clonic convulsion, either generalized or unilateral, was seen most consistently through the entire course, and it continued to the end of follow-up in 11 patients (79%). On the contrary, myoclonic seizure, complex partial seizure, and atypical absence often disappeared and reappeared repeatedly during the course. In SME, seizure symptoms varied widely among patients in comparison with other neurological symptoms, and the most consistent core seizure type was tonic-clonic convulsions.

Transient focal cortical hypometabolism in idiopathic West syndrome

Positron emission tomography (PET) using 18F-labeled 2-deoxy-D-glucose was performed serially in 5 infants with idiopathic West syndrome. While tonic spasms persisted, 2 infants had hypometabolism in the bilateral temporo-parieto-occipital regions, which disappeared after cessation of spasms. In 2 other infants, PET revealed focal hypometabolism in the temporal region a few months after the disappearance of tonic spasms, but subsequent PET studies were normal. PET can detect transient metabolic abnormalities of the cerebral cortex which may be associated with the pathophysiology of West syndrome.

Photosensitive epilepsy in children

We performed a retrospective analysis of 17 children with photosensitive seizures (PSS) who had been followed for more than 3 years (mean: 9 years). PSS were verified in all patients by simultaneous video-EEG monitoring. The seizures were precipitated by flickering stroboscopes (14 patients) or were induced by patients themselves (3) with head-nodding in front of illumination, blinking at television or close viewing of striped patterns. PSS consisted of myoclonic seizures (eight patients), generalized tonic-clonic convulsions (5), partial seizures (3) or atypical absence (1). According to the International Classification of Epileptic Syndrome, three patients were classified as having severe myoclonic epilepsy in infancy and five as having juvenile myoclonic epilepsy. The remaining nine could not be categorized as any specific epileptic syndrome. Children with age of the onset of epilepsy at 7 years or younger tended to suffer intellectual deficit in addition to intractable seizures.

Epilepsies of Neonatal Onset

Although neonatal seizures are classified as an epileptic syndrome with both generalized and focal seizures in the recent classification, etiologies are very diverse. Most neonatal seizures are caused by acute brain insults, and such seizures cannot be called epilepsy, a chronic brain disorder characterized by repeated attacks. In this paper, we evaluated epilepsies of neonatal onset, i.e., neonatal seizures excluding those due to acute brain insults.

Usefulness of PET scan in a child with mesial frontal lobe epilepsy

Positron emission tomography (PET) scan with 18F-fluorodeoxyglucose (18F-FDG) was performed in a 14-year-old boy who had seizures suspected to have originated in mesial frontal lobe. The seizures occurred in clusters and were characterised by a change in the facial expression at seizure onset and complex motor manifestations consisting of kicking, swaying and screaming. Ictal EEG showed rhythmic alpha-waves in the left frontal area association with the ictus. Cerebral CT, MRI and SPECT revealed nothing of significance, but the PET brain scans showed frontal and parietal hypometabolism, which was most prominent in the left mesial frontal lobe. The present case suggests that FDG-PET scanning may be useful for the diagnosis of the mesial frontal epilepsy, when other imaging studies fail to show abnormalities.

Simultaneous VTR‐Surface EEG Recordings of Simple Partial Seizures of Childhood Onset

We examined 62 simultaneous VTRsurface EEG recordings (SVER) of 23 patients with SPS of childhood onset. The patients were referred to our hospital for evaluation and treatment of epileptic seizures. There were 15 males and eight females. The patient age at recording ranged from one to 20 (mean 8.1). The number of recordings per patient ranged from one to eight (mean 2.7). SPS were diagnosed when the patients could respond to verbal stimuli and/or recall events that happened during the seizure. Attacks which evolved into complex partial seizures or secondary generalized seizures were excluded.

Long‐Term Clinicoelectroencephalographic Evolution of Childhood Absence Epilepsy

Childhood absence epilepsy is an epileptic syndrome of children characterized by frequent absence seizures and typical EEG findings. Absence seizures also occur in other forms of epilepsy. A survey of the literature shows that a major difficulty arises in distinguishing childhood absence epilepsy from other epilepsies with absence seizures. In the present paper, the following three aspects are discussed: 1. seizure prognosis and EEG evolution of childhood epilepsies with absence seizures, 2. longterm clinical course of childhood absence epilepsy, and 3. transverse topographical analysis of absence seizures and its predictive value.

Neuroimaging: Early Childhood Prolonged Convulsions and Mesial Temporal Sclerosis Demonstrated by Magnetic Resonance Imaging

Mesial temporal sclerosis (MTS) is found in 50 to 70% of patients undergoing a temporal lobectomy for intractable temporal lobe epilepsy (TLE).’ Magnetic resonance imaging (MRI) is very sensitive in the detection of foreign tissue lesions causing TLE’, but the detection of MTS by MRI has been controversial. Recently Jack et al.4 and Jackson et al.’ reported that MTS can be reliably identified on MRI with a high degree of sensitivity and specificity. Falconer3 noted a significantly increased history of prolonged febrile convulsions in patients with MTS diagnosed by the pathological study after an anterior temporal lobectomy. This study explores the relationship between early childhood prolonged convulsions and the MRI findings of the patients with intractable TLE.