Yoshihiro Naganuma

Auditory event-related potentials in benign childhood epilepsy with centrotemporal spike: the effects of carbamazepine

To clarify the relationship between cognitive function and CBZ therapy, auditory event-related potentials (P300) were examined in 23 patients with Benign Childhood Epilepsy with Centrotemporal Spike (BCECT) compared with 54 normal controls. The results were 1) the mean P300 latency in BCECT (368 +/- 29 msec) was significantly prolonged compared with that in normal controls (349 +/- 30 msec), but most individual patients showed normal values. 2) The prolongation of P300 latency was greatest during the course of therapy. 3) On repeated examination of P300, P300 latency was found to gradually become shorter with age in spite of continuous CBZ therapy. At initiation of CBZ therapy, the P300 latency became shorter; on the other hand, P300 latency became shorter with the discontinuation of CBZ. 4) The age-corrected P300 latency showed a significant positive correlation with the serum concentration of CBZ. Our results suggest that CBZ therapy has both an undesirable effect (chronic impairment) and a desirable effect (improvement of underlying dysfunction caused by epileptogenesis) on cognitive function.

Changes of P300 latency with age in childhood epilepsy

Auditory event-related potentials (P300 latency; odd-ball paradigm) were examined in 129 patients with childhood epilepsies and 53 controls. The P300 latency in the patients with epilepsies (373 +/- 39.4 ms) was significantly longer than in controls (356 +/- 38.4), and the prolongation was greatest in the patients with symptomatic partial epilepsies (390 +/- 40.5), mild in those with idiopathic generalized epilepsies (370 +/- 24.3), and minimum in those with idiopathic partial epilepsies (363 +/- 28.9). Abnormal P300 latency occurred at all ages during childhood in patients with symptomatic partial epilepsies, and at older ages in patients with idiopathic generalized epilepsies. The shortening of latency with age was relatively small in patients with epilepsies compared with controls. These results suggest that the prolongation of P300 latency (i.e., existence of cognitive disturbance) displays characteristic changes with age in each epileptic syndrome.

Effects of antiepileptic drugs on EEG background activity in children with epilepsy: initial phase of therapy.

The effects of antiepileptic drugs (AED) on EEG background activity were evaluated in 37 newly treated children with epilepsy, compared with 46 age-matched healthy controls. Before AED therapy, the children with epilepsy, both partial (treated with carbamazepine, CBZ group) and generalized seizures (treated with valproic acid, VPA group), already exhibited significant slowing of EEG with increased delta and decreased alpha power. Following 3 to 6 months of AED therapy, this EEG slowing was enhanced in the CBZ group and reduced in the VPA group. Following 1 year of AED therapy, an increase in frequency was recognized in the CBZ group. These results suggest that 1) most children with epilepsy already exhibit slowing of the EEG at the onset of seizures, which may reflect CNS developmental deficit, 2) the short-term effects on EEG are different between CBZ and VPA, and 3) EEG development with age continues under continuous AED administration. The EEG background activity in children with epilepsy is affected by many factors, which include the underlying CNS dysfunction of the epilepsy itself and also AED therapy (type of AEDs, duration of therapy, etc).

Event-related potentials (P300) and EEG activity in childhood partial epilepsy

To clarify the relationship between the cognitive function and EEG activity, auditory event-related potentials (P300) were examined in 72 patients with partial epilepsy. Twenty-six patients (67 trials) had idiopathic partial epilepsies (IPE), and 46 (118 trials) symptomatic or cryptogenic partial epilepsies (SPE). For this study, patients undergoing carbamazepine monotherapy with a dose of less than 16 mg/kg/day were selected to rule out the effects of anti-epileptic drugs. The results were as follows: (1) The P300 latency tended to be prolonged in association with the EEG slowing in both epileptic groups. (2) There was no clear relationship between the frequency of paroxysmal discharges and the P300 latency. (3) The P300 latency was slightly prolonged in the patients with temporal foci compared with that in ones with extra-temporal foci. (4) There was no significant relationship between the generalization of focal paroxysmal discharges and the P300 latency. These results suggested that the influence of EEG abnormalities (particularly paroxysmal discharges) on the P300 latency is relatively little, and the cognitive dysfunction in partial epilepsies mainly originates from other factors such as the epileptogenic lesion itself.

Epileptic seizures and event-related potentials (P300) in childhood partial epilepsies

To clarify the relationship between cognitive function and clinical seizures, auditory event-related potentials (P300) were examined in 72 patients (185 trials) with partial epilepsy. Twenty-six patients (67 trials) had idiopathic partial epilepsies (IPE), and 46 (118 trials) symptomatic or cryptogenic partial epilepsies (SPE). In this study, to rule out the effects of epileptogenesis and other factors, we only examined patients with partial epilepsies undergoing carbamazepine (CBZ) monotherapy at doses of less than 16 mg/kg/day. The results were: 1) the mean age-corrected P300 latency in the patients with SPE (394 +/- 38 msec) was significantly prolonged compared with that in the patients with IPE (378 +/- 28). 2) The prolongation of the P300 latency had no relationship to the seizure frequency, seizure type or seizure duration. 3) In both epileptic groups, there was no significant correlation between the seizure-free period and the age-corrected P300 latency. Our results suggest that the effect of clinical seizures on the cognitive function may be relatively little, and that the cognitive dysfunction in partial epilepsies may mainly originate from epileptogenesis or other factors.

Changes in EEG Foci with Age in Childhood Partial Epilepsies

The age changes of epileptic foci on EEG were evaluated in 208 patients with childhood partial epilepsies, who were followed for more than 3 years. 1) The incidence of EEG foci in each region apparently differed with age. Frontal and central foci were frequent before school age and after adolescence. Temporal foci showed a peak around adolescence, and occipital foci a peak from 3 to 7 years, respectively. Parietal foci were rare at all ages. 2) The migration of EEG foci was recognized 171 times in 81 of the 208 patients (38.9%) during the clinical course. The migration was frequently seen at early school age and preadolescence, and the direction of migration was predominantly anterior to posterior at early school age, and posterior to anterior at preadolescence. These results suggest that EEG foci show characteristic changes with age during the clinical course, which may be related to maturation of the central nervous system.

Familial neuronal migration disorder: Subcortical laminar heterotopia in a mother and pachygyria in the son

We describe clinical manifestations and magnetic resonance imaging (MRI) findings in a man and his mother who were diagnosed as having a neuronal migration disorder. The son had severe psychomotor retardation and the mother had intractable seizures and mild psychomotor retardation. MRI demonstrated moderate pachygyria in the son and subcortical heterotopia in the mother. In both patients, the frontal parts of the brain were characteristically more affected than any other areas. A dominant pattern of inheritance in the family suggests a genetic role in the underlying cause of the migration disorder. The difference in severity between the two patients also suggests an X-linked dominant inheritance. Our family fits the condition of X-linked lissencephaly.

Flunitrazepam for sleep disturbance in children with intractable epilepsy

Add-on therapy with flunitrazepam (FNZ) was performed in 5 children with marked sleep disturbance and intractable seizures. Correction of the sleep disturbance was attained immediately after the start of FNZ administration in all patients. Furthermore, a significant decrease in the seizure frequency (3 patients) and improved quality of life (4 patients) were concomitantly observed. There was no adverse effect or interaction with conventional AEDs on long-term use.

Electroencephalogram and Clinical Neurophysiology: The Effect of Anticonvulsants on EEG Background Activity in Epileptic Children with Monopharmacy

The subjects were 66 epileptic children with monopharmacy (CBZ; 39 cases and VPA; 21 cases). The EEG was recorded every 6 months in each patient from the onset (before administration of AED) to one year after discontinuation of AED. The mean ages at starting medication were 8.3f3.0 in the CBZ group and 11.3f2.9 in the VPA group, and those at the final seizure attack was 8.3k2.7 in the CBZ group and 11.0k3.4 in the VPA group, and those at discontinuation of AED was 11.5+2.5 in the CBZ group and 11.8f4.2 in the VPA group. The EEG was taken applying the 10-20 system of electrode placement. The bandpass filters were set at 60 Hz. The EEG was additionally recorded on magnetic tape. Out of 3 min of recording with eyes closed, the EEG sample for an analysis was chosen free of artifacts and paroxysmal judged by inspection. The computerized spectral analysis was done by the record of 0 1 derivations, using Fast Fourier Transformation. Digital conversion was undertaken with 64 Hz. The record was divided into 16 epochs of an 8-sec duration. The spectral analysis resulted in 200 values within 0.5-25 Hz and calculated total power, mean frequency and relative powers in delta (0.5-3.85 Hz), theta (47.85 Hz), alphal (8-9.85 Hz), alpha2 (1012.85 Hz), beta1 (13-19.85 Hz), beat 2 (2025 Hz). The log(X) for both relative band power and total power were evaluated. The changes in the EEG background activity were compared between before and after starting administration of AED, between before and after discontinuation of AED, using the paired t-test. The changes from 6 to 30 months after the final seizure attack was analyzed by 2 way ANOVA in a patient who had not any seizures for at least 30 months.

EEG abnormality in patients with febrile seizures: Cases with the same paroxysmal discharges for more than 3 years

(group A). The results were compared with in the case of febrile Conclusion. A long-term EEG abnormality in the course of FS did convulsions with other etiologies (group B). Group A consisted of 12 not always mean the development of epilepsy, and such an EEG patients, who were followed for 3 to 20 years (average, 9 years and 8 abnormality also changes in the course of FS age-dependently. months). Group B consisted of 600 cases, who were followed for 3 to However, in some patients, these may be related to the risk of later 20 years and 6 months (average, 10 years and 6 months). subsequent epilepsy. Results. The sex ratio, positive family history of febrile convulsions among first degree relatives, cases with mental retardation and total seizure number were not different between the two groups. No patient in group A had a family history of epilepsy, but 20 cases (3.3%) in group B had one. The body temperature at the time of convulsions was higher in group A than group B. Hemiconvulsions, prolonged seizures over 60 minutes and recurrent convulsions were significantly more frequent in group A. The time from the onset of fever to the convulsions tended to be longer in group A, but the difference was not significant. The epileptic discharges appearing before 1 year and 2 months of age were compared between the two groups. In group A epileptic discharges were not noted in any case, but in group B they were noted in 10 cases (16.7%1, all being focal spikes. Single afebrile seizures were not noted in group A, but were noted in 37 cases (6.2%) in group B. One patient in group B (5.7%) suffered from later epilepsy (more than 2 afebrile seizures following febrile convulsions). However, the difference was not significant. Conclusion. Thus, the prognosis of febrile convulsions during exanthema subitum is not so poor, except for some clinical differences from febrile convulsions with other etiologies. Keywords; Febrile convulsion; Exanthema subitum; Epilepsy