The unpredictable fluctuations in plasma levels (Cp) of phenytoin (PHT) were observed in three impatients who received PHT powders from the same lot (PHT (P)). All three patients had organic brain disorders (cerebral infarction, severe mental retardation, porencephaly). One patient with mental retardation was a 5-year-old girl and the other patients were elderly men in poor physical condition.
The fluctuations mentioned above were reduced in size after a change in drug prepartion and Cp was stabilized by the use of PHT granules (PHT (G)) or PHT tablets (PHT (T)).
Through serial intensive monitoring, it was revealed pharmacokinetically that the absorption rate (F) of PHT (P) fluctuated between 0.54 and 0.90; otherwise, F of PHT (G) and PHT (T) stabilized at 0.95 and 0.80, respectively. The pharamcokinetic calculations were based on the assumption that the absorption rate constants (Ka) were 0.2 hr^-1 for PHT (P), 0.5 hr^-1 for PHT (G) and 0.3 hr^-1 for PHT (T) and distribution volume (Vd) of PHT was 1.0 liter/kg. The fluctuations of Cp were explained most reasonably by the changes of F of PHT (P) in all three cases. This was well documented in one patient with a low Michaelis-Menten constant (KM=1.25μg/ml).
Our study emphasizes that intensive monitoring and the use of preparations with stable F are very important for therapeutic use of PHT, because PHT is a drug that shows saturation kinetics under the therapeutic situations.

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Out of 371 epileptic patients followed more than 3 years in our hospital, 254 patients were free from seizures, of whom 195 had a seizure-free period more than 3 years at the last visit and were served as control group. On the other hand, seizures were uncontrolled in 117 patients and in 54 of them, who were classified as intractable group, seizure frequency did not change or even increased at the last visit. The rate of persistent seizures was high in cases with secondary generalized epilepsy (SGE), especially Lennox-Gastaut syndrome or West syndrome. In some of patients with complex partial seizures (CPS), seizures were poorly controlled. In patients with impaired intelligence or with prenatal or perinatal presumptive causes, seizures tended to be uncontrolled.
In control group, initial treatment was effective in 165 of 195 patients (84.6%), whereas seizures were refractory to early and intensive medical therapy in about 2/3 of the intractable group.

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Between January 1980 and June 1985 105 patients were referred to our hospital for refractory seizures. Most of them had frequent seizures belonging to secondary generalized epilepsy or partial epilepsy. The obvious reason for difficulty in seizure control were an error in the diagnosis of seizure types and/or inappropriate use of antiepileptic drugs, such as error of the choice of drugs, polypharmacy, or suboptimal dosage. These errors were seen in about 15% of referred patients. As to the problem on the part of patients, non-compliance, insufficient understanding about treatment of epilepsy, or hypersensitivity to drugs was noted in a few cases. More than 50% of referred patients had no definite reasons for difficulty in seizure control.
Reduction of multiple drugs, intermittent serial rectal or oral administration of diazepam, or high-dose therapy of carbamazepine, henytoin, valproate or others resulted in more than 50% reduction of seizure frequency in 62 out of 105 patients (59.0%) referred for refractory seizures.

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Detailed clinical and electroencephalographic long-term follow-up studies were made on 14 cases (3 boys and 11 girls) of severe myoclonic epilepsy in infancy (SME).
1) Familial predisposition to convulsions was observed in as many as 9 cases (64.3%).
2) Onset of convulsive seizures or characteristic partial seizures ranged from two to seven months of age, and additionally atypical absences and myoclonic seizures appeared at ages between seven months to 4 years 5 months
3) Alternating hemiconvulsions and/or generalized convulsions were observed in 14 cases (100.0%), characteristic partial seizures with ocular deviation and cyanosis in 11 cases (78.6%), atypical absences in 13 cases (92.2%) and myoclonic seizures in 10 cases (71.4%). Convulsive seizures were characterized by being easily precipitated by fever and hot baths, and often occuring in a cluster or status epilepticus.
These seizures were very intractable; at the time of follow-up convulsive seizures were not suppressed in any case and atypical absences and myoclonic seizures were suppressed at between 4 years to 17 years in only 5 cases.
4) Despite almost normal development prior to the onset of seizures, all the cases showed overt slowing in mental development after one year of age.
5) EEG back ground activity deteriorated with age, although mild in infancy.
6) Epileptic discharges were hardly detectable in infancy, while after age one all the cases showed epiletipc discharges characterized by the combination of diffuse(100.0%) and focal (92.9%) epileptic discharges.
7) Photosensitivity and pattern-sensitivity were observed in as many as 7 cases (50.0%) and 5 cases(37.7%), respectively, and clinical seizures were activated by light or geometric patterns in 5 cases (71.4%) of those with photosensitivity and all 5 cases with pattern-sensitivity.
From these findings, SME was suggested to be a specific type of secondarygeneralized epilepsy with characteristic clinical course and remarkably poor prognosis.

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Childhood epilepsy without organic lesion is thought to have a good prognosis, but some cases have relapses after a long seizure-free period. In this study, we studied relapses of seizures clinically.
1) We studied 20 cases who were diagnosed as epilepsy and were treated at the pediatric clinics of Keio University Hospital and 3 affiliated hospitals and had relapses after a seizure-free period of three years or more.
In the majority of these cases, seizures recurred after the age of puberty. Thirteen cases had primary generalized epilepsy which had been thought to have a good prognosis.
The presumptive triggers of relapses were poor compliance of drugs, fatigue emotional stress, acute infective diseases, and menstruation. Of these triggers, poor compliance of drugs was the most important. And only 3 cases had no such triggers.
In 6 cases, the epileptic discharges reappeared in EEG within 2 years after relapses, and it was only in 3 cases that the epileptic discharges reappeared within 2 years before relapses. Therefore, it is difficult to predict the relapses by the use of EEG findings.
2) Two hundred and twenty one epileptic patients with a seizure-free period of 3 years or more were followed for 3 years to 13 years 9 months to know the relapse rate.
Seizures recurred in 14 cases, so the relapse rate was 6.3%: 4.1% in cases on unchanged medication, 10.9% during drug reduction, and 10.7% after withdrawal

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A boy aged 10 years with frequent complex partial seizures during nocturnal sleep was investigated by means of overnight polygraphy.
Interictal EEG showed 2-3 Hz diffuse irregular spike and wave complexes mostly in all areas, that were predominant occasionally in the left frontocentral area.
The following three types of linical seizures were observed: C₁, C₂ and C₃. As to C₁, he automatically moved the upper and lower extremities, and then put on the quilt. As to C₂, a tonic posture preceded the same behavior as in the case of C₁. As to C₃, secondarily generalized tonic-clonic seizures succeeded the same behavior as in the case of C₂. During the clinical seizures, EEG showed no apparent change in the first part and then showed diffuse slow wave bursts in all areas. Successively fast activity followed by spike and wave complexes was seen in all areas when the secondarily generalized seizures occurred.
The clinical seizures occurred frequently within three hours after sleep onset, and all appeared in NREM sleep.
Stage 4 latency was prolonged owing to the frequent clinical seizures, but the amount of slow wave sleep was increased on the whole.

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Triclofos sodium (Tricloryl) is used widely as the most available hypnotics in pediatricn practice, but there have been few reports about its use as an anticonvulsant. We report a girl with refractory epilepsy, including life-threatening status epilepticus, whose seizures responded to triclofos sodium given orally.
She had been in a normal perinatal period until fits commenced at five days of age. There were frequent tonic spasms in series during awake and sleep period. Electroencephalogram showed suppression-burst when awake or asleep, in addition to desynchronization during seizures. These characteristics were corresponded to the early infantile epileptic encephalopathy with suppression-burst of Ohtahara. Her seizures were resistent to various anticonvulsants in combination, and thereafter showed the transition to West syndrome at three months. In 1984, aged fourteen months, she was admitted to our hospital having daily one hundred or more generalized convulsions of up to three minutes duration. These continued despite intravenous infusion of diazepam, phenytoin, gammaglobulin and lidocaine and were not controlled even by intravenous infusion of thiamyral sodium and pancronium bromdie under artificial ventilation. At this stage, triclofos sodium was introduced orally in a dosage of 100mg/kg in every 8 hours, in part for its sedative action. Within three hours of starting the dosage the fit frequency decreased and stopped completely. After three days the dosage of triclofos sodium was gradually reduced and finally withdrawn, but seizures did not recur.
This case report suggests that triclofos sodium may give benefit for children whose seizures are refractory to conventional treatment, especially for those in status epilepticus.

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We reported the rare case of a epileptic who had suffered from clinical attacks since the age of 12 years. In every EEG recorded twenty and several times during 15 years, spike (sharp) and wave complexes or spikes successsively appeared in the occipital region and also σ wave burst appeared predominantly in the frontal region.
The case is a woman of 29 years old, married and full term normal delivery. She had a history of febrile convulsion which was observed one time at ten months after birth. Neurologically abnormal findings, disturbance of sense of sight and disturbance of intelligence were not observed. No abnormality in CT-scan. The pattern of her clinical attack consisted of feeling sick and squating down followed by generalized tonic-clonic seizure. The number of times of clinical attack is eight in total which is a small number considering the appearance of continuous epileptic discharge. Though epileptic discharges were suppressed by eye-opening, they did not disappear with antiepileptics. REM sleep was observed in all-night sleep, however, distinct hump and spindle waves were not observed and σ wave burst often appeared during NREM sleep, which made staging of sleep difficult. Epileptic discharge decreased during REM sleep than during waking state and markedly decreased during NREM sleep. The frequency of epileptic discharge decreased after 27 years old on.
The localization of the lesion was considered to be not in the cortex of the occipital lobe but in the deeper part.

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A TRH analog, DN-1417 has been reported to possess an antiepileptic action (Inanaga et al. 1981). The analog was effective in improving the EEG and producing favorable psychiatric effects such as the activation of facial expressions and a reduction of dyshoria and perversity in some patientswith refractory epilepsy. In this case study, a 20 year-old woman underwent DN-1417 treatment for her auditory hallucination and autistic behavior. She has been diagnosed as suffering from temporal lobe epilepsy.
After a series of injections of 2 mg of DN-1417 for two weeks, her psychomotor activities increased and her abnormal behavior improved, being accompanied by the increased fast activities on the background EEG. Her EEG power spectrum was measured with digital computer (HP-2108 A), using the Fast Fourier Transform.
As a result, her dominant power spectrum sifted to the faster frequency after the DN-1417 treatment.

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