The clinical efficacy of intermittent therapy with rectal diazepam (DZP) suppositories for the prevention of recurrent febrile convulsions was studied. The dosage schedule used for rectal DZP suppositories was based on the results of the pharmacokinetic analysis reported previously.
One hundred and thirty-three children aged 10 months to 4 years with two or more previous febrile convulsions were treated intermittently with rectal DZP suppositories. Suppositories containing 0.5mg/kg of DZP were given rectally to the patients at home as soon as the initial signs of febrile illness were noticed by their parents. A DZP suppository of the same dose was administered again 8 hours after the first dose, when the fever still remained above 38.0°C. The patients were followed closely for 6 to 43 months at our pediatric seizure clinic.
Of the total of 787 febrile episodes above 38.0°C in all patients during the followup period, DZP suppositories were administered to the patients in 722 cases (91.7%), including 47 cases in which DZP suppositories were administered soon after the occurrence of seizures. Thirty-eight of the 133 patients (28.6%) had a total of 58 recurrences of febrile convulsions (7.4% of the total of 787 febrile episodes), of which two recurrences were observed at 7 and 9 hours after administration of the first DZP suppositories, respectively. In 39 cases of the remaining 56 recurrences, the patients were noticed to have fever first after the occurrence of seizures. However, in the cases of the other 17 recurrences, DZP suppositories were not administered to the patients arbitrarily, even if the fever was noticed by the parents before the occurrence of seizures.
No serious side effects except for mild drowsiness and transient ataxia were observed in any of the patients.
Intermittent therapy with rectal DZP suppositories at home seems to be safe and remarkably effective for the prevention of recurrent febrile convulsions, unless the timing of administration is delayed in cases of febrile episodes.

View full abstract

A prognostic study was carried out on 83 cases of the West syndrome followed-up for over three years after the first visit. They were divided into two groups, that is an idiopathic (13 cases) and a symptomatic (70 cases) groups. The criteria for idiopathic cases were as follows: 1) no etiology 2) normal development prior to the onset of tonic spasms 3) no antecedent seizures before tonic spasms 4) no abnormal neurological findings 5) no asymmetry in the hypsarhythmia 6) no abnormal neuroradiological findings.
The mental and seizure prognoses were significantly favorable in the idiopathic group, comparing with the symptomatic. 10 (76.9%) of 13 idiopathic cases and 13 (18.6%) of 70 symptomatic cases were mentally normal, and clinical seizures were controlled in all the idiopathic cases and only 38 (54.3%) of 70 symptomatic cases at the follow-up. Throughout the clinical courses, none of the idiopathic cases and 34 (48.6%) of 70 symptomatic cases evolved into the Lennox-Gastaut syndrome (LGS). Cases evolving into LGS were significantly less favorable in both mental and seizure prognoses, comparing with those without such evolution. This finding suggested that the persistence of seizures may provoke mental deterioration.

View full abstract

It is well known that limbic seizures are more intractable than neocrotical seizures. This evidence is consistent with our previous finding that the seizure susceptibility produced by limbic kindling was more persistent and potent than that of neocrotical kindling. However, further changes in seizure susceptibility resulting from long-term repetition of generalized convulsion in neocortical kindling remians unclear. In this study, we examined a chronological pattern of seizure susceptibility during 100 days of kindling stimulatins (over-kindling sessions, O-KS) and additional daily stimulations after 100 days of stimulus-free interval in Sylvian or Ectosylvian gyrus kindling in cats. The animals were divided into the following two groups based on the stability of kindled generalized convulsion during O-KS, Group-A (n=4): A stable kindled generalized convulsion appeared after repeated stimulations, and Group-B (n=8): the appearance of generalized convulsions was unstable during O-KS. There was no difference in afterdischarge threshold, kindling rate, location of the electrodes in the temporal cortex, or duration ofgeneralized convulsions between these two groups. Interictal spike discharges were recorded only in group-A after 100 days of resting period. Stage-5 generalized convulsions appeared at the first stimulation of R-KS in 4/4 of group-A and 4/5 of group-B. The most dramatic finding was an appearance of recurrent spontaneous generalized or partial seizures originating in the opposite hemisphere or limbic system, which appeared in 3/4 cats in group-A, but none in group-B. These results suggest that a persistent, solid epileptogenecity can be established after repeated generalized convulsions in neocortical kindling, and that secondary epileptogenic change in the limbic system may play a role in it.

View full abstract

Juvenile myoclonic epilepsy of Janz (JME) is one of the primary generalized epilepsy characterized by myocloic seizures and awakening grand mal. In this time we presented 14 cases of JME which we have examined. There are 5 male and 9 female. The mean age at onset of epilepsy was 11 years and 2 months, ranging from 4 years to 14 years and 3 months. The age at onset of myoclonic seizures was ranging from 9 years and 16 years and 4 months, with the mean age of 12 years and 7 months. Period of following up were from 0 year and 7 months to 13 years and 10 months, average period of which were 6 years and 2 months. The different seizures types were observed on 12 cases, which were 8 cases of GTCS and 4 cases of GTCS combined with absence seizures. Positive family history for epilepsy or febrile convulsion was found in 6 cases of patients.
EEG showed the diffuse 3-5 Hz polyspike and waves in all patients and photosensitivity in 8 cases and activation by HV in 10 cases. Their intellectual prognosis were excellent but seizure prognosis was difficult to reffer because of insufficient treatment due to uncorrect diagnosis of parial seizure evolving to GTCS instead of JME in 4 cases. Uncorrected diagnosis of JME might be made from lack of awareness about these characteristic features or poor history taking on the preceding seizures of GTCS. We must pay attention upon the GTCS around the puberty not to miss the subtle preceding phenomenon.

View full abstract

We reported a case, a 10 years old girl, with ESES with infarction of the right thalamus confirmed by CT scan and MRI. She began to have nocturnal hemiconvulsion at the age of 4 years 11 months old and atypical absence and unconscious adversive seizures at the age of 5 years and 7 months old. Overnight EEG recording at the age of 5 years and 11 months revealed that diffuse bilateral synchronous 2-2.5 Hz sharp and slow wave complexes with right hemispheric dominancy continued throughout the period of non-REM sleep without any discernible background activity (sp. w index=95%).
Her seizures gradually became more frequent and abnormal behaviors, the disturbance of short term memory and geographic orientation apeared. Institution of MCT ketogenic diet therapy successfully controlled the above troubles, but the improvement to the ESES was only transient for the period of observation of 4 years and 9 months.
We suggested that a loss of thalamic function may contribute to the genesis of such a rare epileptic condition as ESES and the continuous spike and wave complexes could cause the selective impairment of the higher cortical functions.

View full abstract

An open dose-finding trial on oral administration of DN-1417 was undertaken to investigate the relationship among dose, efficacy and side effects. 190 patients with severe epilepsy resistant to conventional drug treatment were randomly allocate to two treatment groups of low dose (20mg/day for adult) and high dose (80mg/day for adult). Medication was done at fasting once a day for eight weeks. When a satisfactory response did not occur after the first 4-week treatment and the drug was well tolerated, the dose was doubled in the latter half. The global improvement rating (GIR) was made on a 7-point scale (of “markedly improved”, “moderately improved”, “slightly improved”, “no change”, “slightly worse”, “moderately worse” and “markedly worse”) based on seizure frequency, EEG findings and nonparoxysmal clinical manifestation.
GIR was judged as “moderately to markedly improved” in 16% of the patients of the low dose group and in 14% of the high dose group. It was “slightly to markedly improved” in 48% of the patients of the low dose group and in 55% of the high dose group. Thus there was no dose-related difference in two groups. Furthermore, the dose increase was not associated with any increase in the rate of improvement. The rate of the patients judged as “slightly to markedly improved” by GIR was, however, dosedependently higher (lower dose group: 61%, high dose group: 73%) in those with Lennox syndrome having no history of West syndrome. The incidence of side effects was about 20% in both dose groups.

View full abstract

The recent development of single-photon emitting radiopharmaceuticals has introduced a new era for the investigation of neurological disease. We have performed single photon emission computed tomography (SPECT) with ¹²³I-N-isopropyl-p-iodoamphetamine (IMP) to measure regional cerebral blood flow (rCBF) in epileptic children. A total of twenty-four patients with epilepsy were investigated. 4 patients had primary generalized seizures and 20 patients had partial seizures. In 11 out of 20 patients with partial seizures, SPECT revealed a seizure focus, which correlated well with EEG findings. All of these abnormalities in foci were decreased rCBF findings. The relative values of decreased rCBF in foci showed from 67% to 93% compared with those of contralateral regions. The decreased rCBF findings in epileptic foci tended to be more extensive in the patients with organic and/or intractable epilepsy than functional and/or benign epilepsy (Rolandic discharges and occipital spike-waves). This method may be useful to determine the property of epileptic focus as well as localization.
On the other hand, three patients had abnormal organic lesions on x-ray CT scan. These were mild atrophy in the right hemisphere (HHE syndrome), small low density area in the left temporal lobe (old infarction) and diffuse cortical atrophy (due to hypoxic encephalopathy during neonate). The SPECT findings of these lesions showed a marked reduction of rCBF in the more extended area. This method may be also suitable to evaluate the underlying organic and secondarily involving disorders with epilepsy.
These results suggest that the measurment of rCBF by IMP-SPECT is of clinical use for the precise diagnosis and management of patients with epilepsy.

View full abstract

An 8 year-old boy with acquired epileptic aphasia was reported. He had shown mild developmental dysphasia in infancy, but before the onset of the syndrome his speech seemed to be normal. He suffered the first epileptic attack at 6 years 7 months and aphasic symptoms gradually developed after about 7 years 5 months. He showed mutism and was suspected to become deaf at the onset, but did not show verbal auditory agnosia. Electroencephalographically, bilateral midtemporal-dominant slow spike-wave discharges became subcontinuous with more diffuse form during slow wave sleep. Soon after the administration of clonazepam, such epileptiform activities dramatically disappeared. After the normalization of EEG, aphasic symptoms improved slowly and gradually, but articulation disorders such as non-fluency and lack of clarity persisted. The aphasia was mainly expressive and was supposed to be influenced by some developmental factors. The ictal record of hemifacial convulsion during sleep revealed that he had the Sylvian seizure. His type of epilepsy was discussed, and was considered to be related to the benign partial epilepsy in childhood.

View full abstract

A detailed electroclinical analysis was carried out in 15 patients with nocturnal Sylvian seizures followed by a series of minor motor seizures (MMS). The mean age of onset of Sylvian seizures were 4 years and 9 months old and that of MMS were 6 years and 4 months old.
Simultaneous video-EEG recordings or polygraphic recordings carried out in the 6 cases demonstrated the fact that regional rolandic sharp and slow wave complexesand diffusely propagated discharges were coincident with atonic drops of a contralateral upper limb and head nodding of atypical absence, respectively.
Correlation between the onset of the MMS and the initiation of CBZ, which recently stressed by some reports, revealed negative results. With frequent seizures, continuous sharp and slow wave complex were present during sleep. Family history of the epilepsy was found in 5/15 patients.
Some cases were initially medically difficult to manage, but 11 cases, in which longterm follow-up was possible, showed eventual remission of clinical seizures at theage of 8-10 years.
A unique pattern of clinical ictal sequencing and the chronological evolution observed in our series suggest that they should be regarded as an intermediate type between benign partial and secondary generalized epilepsies.
We should also pay attention to the neurophysiological significance of the high voltage sharp and slow wave complexes on the Rolandic area and their diffuse propagation, which would correspond with the partial inhibitory seizures and brief atonic absences, respectively.

View full abstract

Clinico-electroencephalographic features prognostic of poor seizure outcome were studied in 87 children with complex partial seizures (CPS). The clinico-electroencephalographic features of the 38 patients with seizure control and the 49 patients with persistent seizures were compared by chi-square test. The compared clinico-electroencephalographic features were (1) age at onset of seizures, (2) past history of febrile convulsion or status epilepticus, (3) experience of other type of seizures, (4) seizure frequency more than 2 per day, (5) symptomatic etiology, (6) mental retardation, (7) abnormal background activity, (8) focus of seizure discharges. A number of clinico-electroencephalographic features were shown to be of prognostic relevance. The clinico-electroencephalographic features prognostic of poor seizure outcome were (1) age at the first seizure≤2 yr. o., (2) symptomatic etiology, (3) mental retardation, (4) abnormal background activity, and (5) Ti, T2, focus. The number of these clinico-electroencephalographic features in each child related significantly to seizure control. In 21 patients who had no these clinico-electroencephalographic featuress, only 4 showed persistence of seizures. While the persistence of seizures was observed in 82.4%-91.9% of 28 patients who had more than three these clinico-electroencephalographic features.

View full abstract

The analysis of clinico-electrical features was performed on children with ocipital epileptiform discharges, who were followed for more than 5 years. The epileptiform discharges were noted to appear in 23% of patients at the age of 1-10 years (mean, 5 years), and disappear in 48% of cases at the age of 4-13 years (mean, 9 years). About a half of cases revealed some evidence of organic brain lesions, but only 4 of them appeared to have organic lesions localizing in the occipital areas. Seizure types frequently observed were generalized motor seizures, unresponsiveness, vomiting, eye deviation, automatism and/or hemiconvulsion, and visual seizure was documented in 21% of cases with epileptic seizures. In comparison with children with organic brain lesion, a high incidence of febrile seizures and family history of convulsive disorders was noted in 21 cases which showed no evidence of brain lesions. Fourteen of them had been followed up to the age of 15 years, and 8 (57%) demonstrated no epileptic seizures as well as no epileptiform discharges untill that age. This benign group was characterized by an earlier onset of seizures (less than 7 years old), and a higher incidence of family history of seizure disorders, compared with patients whose seizures continued even after 20 years of age.

View full abstract

With a wish to understand the epileptic phenomenon in the immature brain, we compared the development of amygdaloid kindling in kittens with that in adult cats. Five kittens (kitten group) and six adult cats (adult group) were subjected to kindling preparation, and the results obtained were as follows: 1) Although the kindling rates between kitten and adult groups were similar, kittens reached kindling stage 4 quicker and remained longer at stages 4-5. To arrive at kindling stage 4, the kitten group needed significantly fewer stimulations and a shorter AD duration, after which many stimulations and a longer AD duration were needed to arrive at the final stage in comparison with the adult group.
2) The GST of the kitten group was significantly higher than that of the adult group.
From these results, we were able to conclude that the excitatory system should be stronger than the inhibitory system of the kitten limbic structure, whereas the inhibitory system of the generalized epileptic mechanism should be stronger than the excitatory system in the kitten brain.

View full abstract