A case of 31 year old man with intractable frontal lobe epilepsy and probably drug induced ataxia was reported.
CT and MRI showed right frontal cortical atorophy. PET study indiccated low metabolic area on the right anterior region. Scalp EEG suggested the right frontal epileptogenesity. Forty-eight implanted subdural electrodes showed two separate epileptogenic foci on the surface of the frontal cortex which brought out different seizure patterns. The area to be removed most efficiently and safely was determined by series of neurophysiolosical studies and performed extensive right frontal corticotomy. After operation, he had completely been free of seizure without significant functional deficits. He showed marked improvement in daily activity and became to be able to cope with his associates. The control of epileptic seizures resulted in favourable influence upon the mental functions of the patient.

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The author examined driving status in 255 patients with epilepsy (144 males and 111 females) ranging in age between 16 and 59 years.
One hundred and twenty-seven patients (50%) had driven a motor vehicle, four of whom had done without driving licences. At the time of this study, 112 subjects (44%) held current licences and 94 patients (37%) were still driving.
Of the 112 licence holders, only 10 had consulted a doctor about obtaining the licence. Seventy-five of the 112 subjects (67%) had seizure-free period for three years or more at this study.
Thirty-four of the 127 patients (27%) had caused traffic accidents, and nine of the accidents (26%) had occurred due to seizures. Fatal accidents were two, one of which happened as a result of a seizure. Thirty-two accidents, except the above two, were defined as any damage to the driver's car and/or other material damages. Complex partial seizures including secondarily generalized seizures were responsible for eight of the nine accidents (89%) due to fits.

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Adverse effect of phenytoin (PHT) and carbamazepine (CBZ), alone and in combination, to the patients with temporal lobe epilepsy, was discussed. Impairment of smooth-persuit eye movement (SPEM) was used as an indicator for the adverse effect of the antiepileptic drugs. SPEM was examined simultaneousl with measurement of serum concentration of PHT or CBZ at more than three different points in each patient. The mean correlation rate between serum level and threshold of SPEM was -0.94 in six cases with PHT and -0.55 in four cases with CBZ monotherapy. Despite inter-individual variation, the positive inverse-correlation between SPEM threshold and serum level of the antiepileptic drugs was found intra-individually, especially in patients with PHT monotherapy. The process of impairment of SPEM was nearly parallel with increase of serum level. In combination therapy, a higher degree of impairment of SPEM was observed than in monotherapy with each of them. In one case, whose SPEM was measured at four different points during PHT alone, four pointts during CBZ alone, and two points during PHT and CBZ in combination, supra-additive impairment of SPEM was observed in combination therapy.

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KW 6066 N, a new slow-release preparattion of valproic acid (VPA) which was developed in Japan, and the conventional VPA were administered in each to ten healthy male volunteers, and their pharmacokinetics were analyzed.
1) There was a time lag of approximately two hours in absorption of KW 6066 N, with slow absorption curve. The Tmax was at approximately ten hours after ingestion.
2) The ratio of free fraction was increased as the total level increased, irrespective of the difference between the drug types. The %-free fraction was in proportion to the total level.
3) Statistically significant differences were evidenced in pharmacokinetic parameters including Ka, Tmax and Cmax. No differences, on the other hand, were observed in such parameters as Ke, Vd, T_1/2 and AUC.
4) The pharmaceutical characteristic of KW 6066 N was deemed to be retardation in the rate of bioavailability.

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Epileptiform EEGs which were defined as having spike, sharp and spike-wave, but excluding diffuse spike-wave in drawsy state in children with febrile convulsion (FC) have been evaluated by a comparison of 120 epileptic children having histories of FC (Epi) with 80 FC children having epileptiform EEGs (EFC). Main, statistically significant findings in EEGs between Epi and EFC, which were considered as risk factors of epilepsy in FC, were as follows:(1) Epileptiform EEG having both focal and diffuse epileptic discharges (p<0.01), and multifocal epileptic discharges (p<0.05) in the first abnormal EEG, (2) high frequent epileptiform EEG in the follow up EEGs, and (3) having both focal and diffuse epileptic discharges in the same record. Among 24 FC children having epileptiform EEGs had been followed up without medication to at least 10 years old, eight out of them (33.3%) manifested non-febrile seizures in the follow up duration. Thus the epileptiform EEG in FC children seems to indicate an important risk factor for developing epilepsy.

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Slow-release sodium valproate (VPA) tablets currently under development were administered q. d. orally to 8 healthy volunteers and 13 patients with epilepsy. Results: 1) The diurnal variation of VPA concentrations in volunteers at day 6 of dosing at 1, 200mg/day q. d. was 65% after once-daily administration as againts 19% with twice-daily doses. 2) In 2 patients receiving twice daily therapy, the diurnal variation was 20% and 18% respectively, agreeing well with the corresponding values in volunteers. 3) The diurnal variation pattern of level/dose ratio in patients receiving once or twice daily monotherapy agreed well with that observed in volunteers. 4) Complete seizure control was 100% for 4 patients with primary generalized epilepsy, 43% for 7 with partial epilepsy and 0% for 2 with secondary generalized epilepsy, and these values were assumed to be virtually the same as those obtained with ordinary VPA tablets. 5) Of all patients in whom complete seizure control could be achieved with the test drug, 5 of 7 patients were given the drug once daily.
These results clearly demonstrate that slow-release VPA tablets have remarkably stable pharmacokinetic features and are capable of yielding therapeutic efficacy even when administered in a single daily dose.

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The authors carried out ictal EEG and/or simultaneous EEG and video tape recordings in 7 patients with benign infantile convulsions (Fukuyama, 1963) and analyzed the ictal phenomenon in detail. The study demonstrated that seizures in 5 of 7 cases with this condition, which had been considered to be of apparently primary generalized, turned out actually to be of secondarily generalized one. The interval between the start of paroxysmal discharges at a certain limited area to its full generalization ranged from about 20 to 40 seconds. The sites, from which ictal discharges began to appear on the EEG, were the unilateral temporal area in 4 cases and the frontal area in 4 another one. In the rest two cases, focal onset of epileptiform discharges was difficult to be recognized, partly due to the mixture of body movement artifacts and partly due to the short interval if any present.
Since only the latter 2 cases were accompanied with diarrhea at the time of convulsions, it cannot be denied the possibility that neurophysiological mechanism of convulsions in the diarrheic infants might be different from that in non-diarrheic infants.

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The development and propagation of epileptic spikes in feline thalamic penicillin.(Pc) epilepsy were studied electrophysiologically. A concentric bipolar stimulating electrode with canula was inserted into the ventro posterolateral nucleus (VPL) of the thalamus at cordinates A: 9, H: 1, L: 6 of the atlas of Jasper and Ajimone-Marsan (1954) stereotaxically in 50 adult cats. Epileptogenic focus was induced in the left VPL by means of local injection of benzylpenicillin potassium (10μl), Electroencephalograms (EEG) were recorded from both hemispheres and VPLs. Changes of EEG recorded from the left VPL after the application of Pc were classified as stage I (phase of sporadic spike dicaharges), stage II (phase of frequent spikes and polyspikes) and stage III (phase of volley of ictal discharges). Stage III were established 32 in 38 cats (84%), utilizing aqueous Pc (1×10⁶U/ml). The average time lag from injection of Pc to stage 11 was 57±39 miniutes. The ictal discharge was originated in the VPL of Pc injection side, then propagated to the ipsilateral primary somatosensory area and to the contralateral VPL, simultaneously, and finally spread to the whole brain. It was necessary not only to section of the corpus callosum but also to section of the massa intermedia to block the propagation of ictal discharges to the contralateral VPL and cerebral hemisphere. The results of this experiment imply that the massa intermedia of the thalamus as well as other cerebral commisures play a very important role in the propagation of epileptogenic discharges in cats.

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The present study was especially undertaken to investigate the effects of penicillin (Pc) induced thalamic focus on short latency somatosensory evoked potentials (SSEP) by the median nerve stimulation and cortical response (CR) by stimulation of the ventral posterolateral nucleus (VPL) of the thalamus. Details of the model should be refered to part 1. Changes of EEG recorded from VPL after the application of Pc were classified as Stage I (phage of sporadic spike discharges), II (frequent spikes and polyspikes) and III (volley of ictal discharges). SSEP normally consisted of a large positive (P) wave (the maximal peak latency: 7.1±0.6 msec) in VPL and P₁ (9.4±0.9 msec) and N₁ (14.1±0.8 msec) in the primary somatosensory cortex (SI). CR normally consisted of two small negative waves (n₁: 1.3±0. 4 msec, n₂: 3.2±0.4 msec), followed by a large negative wave (n₃: 6.8±0.8 msec). The components of SSEP and CR at stage I and II revealed no remarkable changes. On the other hand, the latency of P1 had prolonged and N₁ disappeared at ictal stage of stage II. The latency and amplitude of n1 and n₂ revealed no remarkable changes but n₃ was disappeared or reversed to positive at ictal stage of stage III. The amplitude of P-wave decreased but not disappeared at ictal stage. In interictal stage, SSEP and CR returned to normal patterns. These findings of SSEP and CR were similarly obtained either in the hemisphere of Pc injection or non-injection sides. It is suggested that the finding of disappearance of N1 may be due to a block of the thalamocortical projection.

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