For the purpose of topographical analysis concerning EEG in epilepsy, we developed a method of dynamic topography, in which interspike interval histogram and computerized topography of EEG were combined.
Twenty-four-channels EEGs including sixteen channels out of the international 10-20 system and eight channels on bilateral paramedian lines, were recorded by the monopolar derivation. At first, EEG spectral analysis was carried out using fast Fourier transformation technique. The spectral data in each frequency band of each channel were stored in data tape as an equipotential EEG topography of square roots of powerspectra. And then, interspike interval histograms were made in each channel and stored in data tape. Finally, both EEG topography and corresponding histogram were superimposed in one display, which was successively demonstrated on the monitor TV of twenty colors. A clinical application in case of focal epilepsy was presented.
Our display made it possible to analyze sequentially dynamic correlation between epiletogenic discharge and basic activity.

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Adult epileptic patients were classified into three groups by their seizure types and clinical courses, and background activities of their EEGs were analysed by the computerized wave form recognition method.
The subjects were 54 cases in total: eight cases of tonic-clonic seizures of primary generalized epilepsy (P-GTC), 46 cases of complex partial seizures of partial epilepsy (CPS). P-GTC (-)(8 cases) and CPS (-)(11 cases) were groups of patients showing the favorable clinical course for the past over three years without any seizures prior to the EEG recording respectively. CPS (+)(22 cases) was a group of patients showing the unfavorable clinical course with some seizures within three years. The control group was consisted of healthy adults (306 cases) of the same age range.
Results:
1) By comparison between P-GTC (-) and control, the % time beta of P-GTC(-) was significantly higher than that of control. By comparison between CPS andcontrol, the % time alpha of CPS was lower than that of control and the % time thetaand beta of CPS were higher than that of control. The average amplitude of theta ofCPS was higher than that of control.
2) By comparison between P-GTC (-) and CPS (-), the % time theta of CPS (-)was significantly higher than that of P-GTC (-) at Fp 1. By comparison between P-GTC(-) and CPS (+), the % time theta of CPS (+) was higher than that of P-GTC (-)at Fp 1, C 3, O1 and the % time alpha of CPS (+) was lower than that of P-GTC(-) at Fp 1, C 3. The % time theta of CPS (-) and CPS (+) was interindividuallydispersed more than that of P-GTC (-).
3) There was no significant difference in the % time and the average amplitude ofalpha, theta and beta waves between CPS (-) and CPS (+).
4) Most of P-GTC (-) showed normal background activities. On theo ther hand, the background activities of CPS (-) and CPS (+) showed wide variations from normalto abnormal and there was no correlation between background activities and clinical coursesin CPS.
5) There was no significant correlation between the total units of drugs per dayand background activities of their EEGs. A detailed study, however, should be required to investigate the relation between drug and EEG.

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Clinical features, EEGs and cranial CT scans were analysed on 39 patients with convulsive seizures in the cerebrovascular diseases.
The results were as follows: 1) Of the 946 patients with the cerebrovascular diseases, convulsive seizures were observed in 39 patients (4.1 per cent). Early seizures occurred at the stroke or within the first two weeks in 17 patients. Late seizures occurred after the second week in 22 patients.
2) Both seizures differed from each other in the underlying cerebrovascular diseases, neurological deficits, onset of the seizures, frequency, seizure type and effect of antiepileptic drugs.
3) Seizures following cerebral infarction mainly represented as late seizures, and twothirds of these patients developed chronic epilepsy.
4) From the study of cranial CT scans, it is suggested that the presence of cerebral cortical lesions may be also essential for generation of this late seizure.

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Medication regularity or compliance was investigated on 71 out-patients with epilepsy, treated for 10-15 years.
The results were as follows:
1) At the time of the study, irregular medication were found in 44% of the subjects.
2) One of the most important factors, giving influence on medication regularity, appeared to be seizure control; namely, poor compliance was found more frequently in the seizure-free patients than those with uncontrolled seizure and the difference between them was statistically highly significant.
3) Long duration in the therapy tended to deteriorate medication regularity.
4) Investigating history of the drug therapy in the individual cases, it was found that some events in life, such as employment, marriage, childbirth and so on, could give significant influence on medication regularity.

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We could completely withdrow all barbiturates from 17 patients with intractable secondary generalized epilepsy (SGE). Vast majority of patients with SGE have been treated under polytherapy including barbiturates. These drugs may have potentially toxic effect through interactions when administered with valproic acid (VPA). The first choice drugs for SGE have been considered as VPA and benzodiazepines. The bioavailability of VPA is reduced by co-existence of barbiturates. Patients frequently complain sleepiness when these drugs are co-administered, and the influence for vigilance by this may lead to increased seizure occurrence.
Dosage of VPA were adjusted in the range of 100-150 μg/ml. Barbiturates were gradually decreased and discontinued finally. After six months of follow-up, mean number of prescribed antiepileptic drugs changed from 4.4 to 2.6 (mainly VPA, clonazepam, and carbamazepine). Thirteen patients (76%) reported reduced seizure frequency at least 50% or more. Also, psychological and physical conditions were improved in majority of patients.
During this trial, the level-dose ratio of VPA was studied. This ratio reduced gradually with augmentation of dosage. The distribution of blood ammonia levels ranged from 13 to 118μg/dl.
Barbiturates are not necessarily required in drug therapy of SGE, andmaybe safely withdrawn.

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Clinical effects and plasma levels were investigated in a prospective randomized study when clonazepam (CZP) was given as a single drug to children with partial seizu es.
The patients included 40 previously untreated children aged 3 to 14 years with any of simple, complex or secondarily generalized partial seizures, who had been newly referred to our pediatric seizure clinic. No patients showed evidence of mental retardation or other associated neuropsychiatric handicaps.
Daily dose of 0.025mg/kg of CZP was introduced and the dosage was increased gradually to the initial maintenance daily dose of 0.1mg/kg. CZP was prescribed in two divided doses per day. Blood samples for determination of plasma levels were taken 2 to 4 hours after the morning dose.
The initial maintenance daily dosage of CZP (0.10±0.01mg/kg) gave plasma levels of 42.9±7.7ng/ml.
Of the total of 40 patients seizures were not controlled in 6 patients on CZP monotherapy. Seizures were increased in 2 patients and behavior changes requiring discontinuance of the drug occurred in another 2 children. However, for the periods of treatment (mean 24.2, range 14-43 months from the onset of CZP therapy) complete seizure control was obtained in 30 out of 40 patients on the initial maintenance dosage, except for 2 patients whose dosage was decreased to tolerable levels because of continuous complaint of drowsiness.
As a wide range of plasma levels (35.0-64.8ng/ml) was associated with complete freedom from seizures, and the plasma levels of patients who did not respond to or had side effects with CZP also falled in the same range, it was not possible to define a therapeutic range for CZP.
In 22 out of 30 patients who responded well to CZP monotherapy, abnormal paroxysmal discharges on the EEG had disappeared after 6 months of therapy.
CZP may be effective in partial seizures as a single and primary anticonvulsant.

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Serial EEGs and clinical symptom changes were reported in a 9-year-old boy with complex partial status epilepticus. Ictal EEG showed a train of repetitive spikes in right post-temporal region followed by generalized slowing, and the clinical symptom was complex partial seizures (CPS) with oral automatism. During the 35 minutes, when both clinical seizures and ictal EEGs were fully recognized on the VTR-EEG monitoring system, seven CPSs (each seizure prolonged 2 to 4 minutes) repeated, and in the interictal phase, there was no full-recovery of consciousness. With intravenous administration of DZP, both clinical seizures and EEG abnormalities subsided promptly. His mental and behavioral state frequently fluctuated, but he recovered completely 7 days after the initiation of confusional state. Seven days after the full-recovery, auditory and visual hallucination developed, but it subsided insidiously 3 days later. This psychic symptom was presumed to be “forced normalization”.

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Carbamazepine (CBZ), its 10, 11-epoxide (CBZE) and trans-10, 11-dihydrodihydroxy-CBZ (CBZ-diol) in serum were measured simultaneously by high pressure liquid chromatography in 48 patients treated with CBZ and in 19 received combined treatment of CBZ and sodium valproate (VPA).
Obtained results are as follows.
1) In patients with monotherapy, the raito of CBZE/CBZ showed linear correlation to the dose of CBZ (mg/kg).
2) In patients with combined therapy of VPA, there was a significant correlation between the ratio of CBZE/CBZ and serum levels of VPA. And, the ratio of CBZE/ CBZ was higher in patients with combined therapy of VPA than with monotherapy.
3) The ratio of CBZ-diol/CBZ was higher in a group of combined therapy of VPA than with monotherapy, but the ratio of CBZ-diol/CBZE showed no difference between two groups.
These results suggested that VPA accelerated the epoxidation and had no influence on trans-diol formation in the metabolism of CBZ.

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We had reported that the long-lasting photosensitivity was observed as a result of kindling in the lateral geniculate body (GL). In the present study, the effect of an intermittent photic stimulation (IPS) on electroencephalographic and behavioral seizure activity was examined under thiosemicarbazide (TSC) administration in the GL-kindled cat. The amygdaloid kindled cat and the electrode-implanted, unstimulated cat was served as a control. TSC, which reduces activity of glutamic acid decarboxylase and lowers brain GABA content, was injected intravenously. IPS at 15f/s was repeatedly applied 0.5 to 5 hours after the injection of TSC.
The GL-kindled cat began to display the IPS-induced myoclonus of the face or neck within 60 to 90 minutes after the injection of 2.5 mg/kg of TSC. The myoclonus associated with spike and wave or polyspikes and wave discharges was provoked up to 5 hours in our observation period. When 5 mg/kg of TSC was injected, the myoclonus induced by IPS became more potent in severity and the generalized tonic-clonic convulsion was triggered by IPS in all of the GL-kindled cat. In contrast, most of the control cat did not show any seizure manifestation under the same doses of TSC.
The present results support our previous report that GL kindling results in a marked photosensitivity and they suggest that the GABAergic mechanism might participate in IPS-induced seizure and photosensitive epilepsy. A possible neural mechanism underlying photosensitivity was discussed.

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Somatostatin (SRIF), which consists of 14 amino acids, has been proposed to have an important role in the experimental models of epilepsy. The direct effects of the intracerebroventricular injection of SRIF were investigated on the cortical EEG and behavioral manifestations to test this hypothesis.
In order to provide some informations of the structure-activity relationships, the activity of authentic SRIF was compared with those of structurally related peptides; Tyr¹-SRIF, Tyr⁸-SRIF, and another endogenous SRIF-related peptide: SRIF (28. SRIF and its analogs were injected to the rats through the cannula chronically implanted in the third ventricle.
1) SRIF, Tyr¹-SRIF and SRIF 28 induced generalized tonic seizures in 18%, 25%, and 33%of the rats tested, respectively. The injections of the peptides also elicited some behavioral abnormalities which were described as barrel rotation and akinesia.
2) SRIF 28 was found to have the most potent activity among the peptides tested in terms of both behavioral and EEG changes.
3) Tyr⁸-SRIF known to be biologically inactive induced no change, suggesting the importance of central portion of the SRIF-structure.
These results suggest that SRIF and SRIF 28 have specific activities to induce seizure with EEG spikings.

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