We report on a 6 1/2 year old boy suffering from complex partial seizures and frequent attacks of atypical absence seizures associated with the transient impairment of the parietal cortical function. During periods of frequent attacks, EEG revealed frequent bursts of generalized 2-2.5 Hz sharp and slow waves complexes maximum over the centroparietal region corresponding without any discernible seizures in wakefulness. When the discharges becme more generalized, they corresponded with brief blinking and unresponsiveness, and on a few occasion momentary dropping of right arm. During sleep, the discharges became nearly continuous and more generalized. He showed gradual deterioration in reading, writing, design copying (constructional apraxia) and impairment of left right orientation. Neuropsychological assessment revealed selective impairment of visuo-spatial perception, visual cogniton and calculation. These abnormalities improved dramatically as the seizure control and the improvement of EEG were established by treatment.
These observations suggest that sharp and slow wave complex cause the inhibition of the underlying cortical function. This result might lead to the concept that the “absence” is not caused by the involvement of the “centrencephalon” (impairment of consciousness) but by the transient inhibition in some of voluntary motor activity, cognition, perception, memory, and affect on the cortex.

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Repeated spaced injection of an initially subconvulsive dose of cAMP into the rat amygdala (AM) produced progressive seizure development similar to electrical kindling. The chemical kindling was accomplished in a dose dependent manner. Furthermore, when combined with EDTA, an inhibitor of phosphodiesterase which catabolizes cAMP, the seizure development was remarkably facilitated. When the animals which had been chemically kindled were subjected to electricl kindling, very rapid seizure development was observed.
In the previous study, we have demonstrated that AM electrical kindling in rats or rabbits resulted in a sustained increase of cAMP in the AM and related brain areas. Taken together, it is suggested that cAMP is involved in both the seizure development and the maintenance of seizure susceptibility induced by AM electrical kindling.

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Recent studies indicate that the substantia nigra (SN) is an important site for the neurocircuitry involved in the modification of various experimental epilepsy models. We hypothetized that this nigral influence on seizures is relayed to next other sites through the r-aminobutyric acid (GABA) ergic projection. To clarify this, the influence of GABAergic activities of SN and target sites of SN efferents-pedunculopontine nucleus (PPN) and superior colliculus (SC)-on pentylenetetrazol induced seizures were assessed in rats. Bilateral administration of GABA agonist (muscimol) into SN significantly suppressed the seizure development; administration into PPN signifiantly facilitated the seizure development; administration into SC did not alter the seizure development. On the other hand, infusion of GABA antagonist (bicuculline) into PPN revealed a protective effect against seizures.
These results indicate that SN and its GABAergic projection to PPN play an important role in the seizure propagation. Thus, PPN neurons may be a key station for the generalization of convulsive activity.

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In this study, we have evaluated the efficacy of a concomitant therapy of CBZ with PB on 10 patients who had been treated with conventional polytherapy of anticonvulsants without satisfactory control, and also resistant further to CBZ alone or higher dose of multiple anticonvulsants including CBZ.
The average age of these 10 patients (4 males and 6 females) was 36.2±15.5 old. The average age of initial onset was 14.4±13. 7 old. Their type of seizures was complex partial seizure in all of them.
Results:
(1) As to the therapeutic results of concomitant therapy of CBZ with PB, the complete disappearance of clinical seizures was observed in one patient, reduction of the frequency by more than 75% in one, reduction by more than 50% in one and no response in 7.(2) As to the electroencephalogram (EEG), abnormal (epileptiform) EEG discharges disappeared in 2 patients. In one of them, seizures disappeared completely and in another, they were controled by more than 75%. Eight patients showed no change.(3) Relevant past history and abnormal CT-scan were not observed in these with improvement, but present in 4 out of the 7 patients without response.(4) The average dose of PB was 100 mg/day (its plasma concentrations 15.3 μg/m) in the clinically improved patients, 200 mg/day (its plasma concentration 31.3 μg/m) in the patient with a reduction of the seizure frequency of more than 75%, 150 mg/day (34.5 μg/m/) in the patient with the reduction of more than 50%, and 214 mg/day (30.8 μg/ml) in the 7 patients who did not respond to the therapy.
This study revealed that a concomitant therapy of CBZ with PB was effective in 30% of the patients with complex partial seizures which were resistant to mono-therapy of CBZ. Our study sugests further consideration of efficacy of a concomitant therapy with two drugs of a various type.

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Magnetic resonance imaging (MRI) and CT were performed on 27 patients with intractable complex partial seizure. The patients'age ranged from 8 to 24 years (mean 14), and the duration of illness varied from 3 to 20 yearrs (mean 8.2). MRI was performed on Picker International (0.5 tesla) and CT on Toshiba (TCT-20A).
Two patients exhibited abnormal MRI, but no analogous abnormalities had been found on CT. One of them showed increased signal intensity area on long SE pulse sequence and decreased signal intensity area on IR pulse sequence in the right posterior temporal lobe. Another showed increased signal intensity on long SE pulse sequence in the right mesial temporal lobe.
CT and MRI were abnormal in 9 patients. Two of them showed low density areas on CT, but abnormalities were found in other areas on long SE pulse sequence. In other two patiens, MRI demonstrated abnormality more clearly than CT. They were suspected to have arachnoid cyst.
CT and MRI were normal in other 16 patients.
These data indicate that MRI is more informative than CT in complex partial seizure. We think that MRI should be used in patients with intractable complex partial seizure.

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The effect of surgical intervention of hippocampal pathway on the epileptic transfer to the contralateral amygdala was examined in amygdaloid kindling model of epilepsy. Sixteen adult cats were used. The animals were received electrolytic lesioning of the ipsilateral ventral hippocampus (5 cats) or fornix (5 cats), or commissural bisection (6 cats) prior to primary site amygdaloid kindling. 1) Epileptic transfer was inhibited by complete electrolytic destruction of mossy fibers (4 cats), but not by partial destruction (1 cats). 2) Commissural bisection inhibited epileptic transfer in 3 of 6 cats, but there was no correlation with the extent of bisection of the corpus callosum or hippocampal commissure. Rather, it was correlated with the destruction of ipsilateral fornix. 3) Epileptic transfer was inhibited by complete destruction of the ipsilateral fornix (4 cats), but not by partial destruction of the fornix or corpus callosum (1 cat). These findings indicate that the hippocampal pathway including mossy fibers and fornix plays a critical role for epileptic transfer to the contralateral amygdala induced by amygdaloid kindling, and that transsynaptic changes through hippocampal pathway may play a role for the development of intractable epilepsy.

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We studied the clinical characteristics of elderly patients with epilepsy, and conducted analysis on their social adaptability.
One hundred and nine patients (male 64, female 45) aged 50 years or above at the time of the study were followed up form more than 5 years. They were diagnosed as follows: symptomatic localization-related epilepsy in 79 patiens (temporal lobe epilepsy 70), idiopathic generalized epilepsy in 21, symptomatic generalized epilepsy in 5, and others in 4.
The mean age at the onset was 24.7 years old, and the total duration of epilepsy was 32.6 (7-65) years, in which that of generalized epilepsy (37.1 years) was longer than that of localization-related epilepsy (31.0 years).
Seizure outcome was favorable in the majority of patients, while 22% of them were found to be therapy-resistant. The majority of the refractory cases had temporal lobe epilepsy whose representative seizure type was complex partial. This agrees with the other studies hitherto reported, while it is notable that there exist some cases of idiopathic generalized epilepsy whose seizures still persist.
Although the social adaptability was found to be good in most of the patients, about 10% of them required custodial care, whose handicap was not only due to epileptic seizure itself but also to physical as well as psychological impairments.

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We report five children (1 boy, 4 girls) with photosensitive partial seizures. They had recurrent partial seizures which were induced by environmental light or stroboscopic test. The onset ranged from 3 to 12 years, and no one had the abnormality of the psychomotor development and neurological finding, except for the seizures. On the interictal EEGs, photoconvulsive responses were observed in all and focal spikes in 3. The ictal EEG was recorded during photic stimulation in two patients. In both of them, rhythmic spikes started in the occipitl area. The other three children had visual seizures represented by visual loss or flickering light on the sight, which were followed by generalized motor seizures, adversive seizures, vertigo and eye lids flutter. The clinicoelectrical features observed in our case seem to suggest that the abnormal discharges may originate only from the occipital area in photosensitive partial seizures, which was also mentioned by Jasper.

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Comparative pharmacokinetic study of a new slow-releasing preparation of sodium valproate (KW-6066 N) was carried out in 8 healthy volunteers. When pharmacokinetic parameters were compared between this slow-releasing tablet and marketed valproate tablet (Depakene) after 600 mg single dose administration, there were difference in Vd, Lag time, Tmax and Cmax, but no difference was found in Kel and AUC between these two drugs. Both of these drugs were comparable to the extent of biavailability, but not comparable to the rate of bioavailability, demonstrating delayed absorption of the slowreleasing tablet. There were no effects of food on the slow-releasing tablet, but there were differences in absorption rate of marketed valproate tablet. When steady state serum levels after multiple dose administration of KW-6066 N were simulated, the diurnal fluctuation of serum concentratin was very a little in twice daily doses and slightly large in once daily doses. However the variations of concentrations in these administrations seemed to be permissible capacity from the viewpoint of expectation of therapeutic effects of KW-6066 N.

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A nine-year-old boy experienced recurrent episodes of impariment of consciousness accompanied by oral automatism and fine rhythmic movements of toes. rIctal EEGs were composed of three different patterns as follows:
1) Rhythmic high voltage slow wave bursts which are often accompanied by small spikes.[Type A]
2) Symmetrical generalized 3 c/sec spike and wave complex preceded by right midtemporal-occipital slow wave bursts.[Type B]
3) Symmetrical generalized 3 c/sec spike and wave complex preceded by very short duration of mid-temporal spikes, not preceded by slow wave bursts. This 3 c/sec spike and wave complex is not terminated abruptly.[Type C]
From the above-mentioned ictal EEG patterns and their corresponding clinical symptoms, this boy is diagnosed as having both complex partial seizure in type A ictal EEG and seizure with secondary bilateral synchrony in type B ictal EEG which slightly resembles absence seizure. But an attack showing type C ictal EEG is difficult to classify. According to the previously reported facts that include the differential diagnosis of absence and complex partial seizures, this seizure is compatible with absence seizures. But considering that this boy was diagnosed as complex partial seizure in type A ictal EEG and a seizure with secondary bilateral synchrony in type B ictal EEG, and phenytoin monotherapy was effective, an attack showing type C ictal EEG should be classified as one indused by secondary bilateral synchrony.

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In order to examine the hypothesis that dysfunction of GABAergic system in the amygdala is related to the development of amygdaloid seizure, an GABA antagonist, bicuculline methiodide, was injected into the amygda of rats. Chemitrodes for both micro-injection and EEG recording were implanted into the left basolateral amygdala. Two weeks after surgery, the animals received single intra-amygdaloid injection of a large dose of bicuculline (10nmol) or repeated (every fourth day) injections of a small dose of bicuculline (0.2or O.4nmol).
The results were as follows. 1) In rats given a large dose of bicuculline, single injection elicited repetitive partial motor seizures which continued for over 60min. Finally, the epileptiform seizure developed to clonic generalized convulsions. 2) In rats given a small dose of bicuculline, repeated injections caused a progressive seizure development which was comparable to that seen in electrical kindling. The animals finally showed clonic generalized convulsions by the application of 5. 3 injections. 3) Histological examination showed prominent neuronal loss in some brain areas such as the bilateral hippocampi and pyriform cortices in the animals that had received the large dose of bicuculline. On the other hand, no histological changes specific to the antagonist injection was detected in the animals that had repeatedly received the small dose of the agent.
The present experiment indicates that suppression of the GABAergic function in the amygdala causes epileptiform seizures and that chemical kidnling is readily induced by repeated injection of a small dose of bicuculline.

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