The epilepsy study of John Huhlings Jackson is being reveiwed and commented on from the perspective of its brilliant contributions to present-day epileptology. His key insights are summarized as follows:
He has challenged the reasonless distinction between true epilepsy (“genuine” epilepsy of authorities) and epileptiform convulsions (Bravis-Jacksonian epilepsy) and abandoned it as an unviable theory. True epilepsy was removed from its provileged position as one epilepsy and degraded to one of the epilepsies. A new conception of epilepsy is constructed by Jackson which includes true epilepsy, epileptiform convulsions and other varities of epilepsies. This new conception of epilepsy is based on his definition of epilepsy: epilepsy is the name for occasional, sudden, excessive, rapid and local discharges of grey matter. There are various pathological causes of epilepsy and many different patterns of epileptic seizures, so in this meaning epilepsy is not singular but plural. As the International Classification of the International League Againat Epilepsy in 1985 proposed, there are clinical manifestations of various epilepsies and epileptic syndromes. Epilepsy, nonetheless, is singular, because every epilepsy, if it be epilepsy, has one functional nervous disorder, that is, “excessive discharges of grey matter”, according to Jacison's paradigm. The raison d'etr of epileptology should be sought at this point.

View full abstract

We investigated the short-term effect of thyrotropin-releasing hormone (TRH) for intractable epilepsy in childhood. The subjects were 10 patients with epilepsy aged 7 months to 12 years. The type of epilepsy were Lennox-Gastaut syndrome (LGS) in 5 cases, infantile spasms in 3 cases, and other secondary generalized epilepsy in 2 cases. All patients had mental retardation of various degrees. The frequency of seizures was more than one a day or more than one a week. Three of the subjects had not received any therapy prior to the TRH therapy.
The daily dose of TRH-tartrate 0.5 or 1 mg was given intramuscularly for two weeks.
Complete control of seizures was achieved in 5 patients and a more than 50% decrease in seizure frequency was observed in 3 cases within 4 to 10 daysafter the initiation of the TRH therapy. No significant change of seizure frequencywas observed in the remaining 2 cases. Electroencephalographic improvement wasobtained in 6 cases during the TRH therapy. In four of the 6 cases responded, seizure discharges disappeared. It was notable that both complete control of seizures and disappearance of seizure discharges on EEG was observed in 3 of 5 cases (60%) with LGS.
Improvement of various degrees in psychic activity was also achieved in all cases. However, transient vomiting, fever and increased irritability appeared in a few infant cases. No other serious side effects were observed during the TRH therapy.
The results of the study indicated that TRH was considered a possible new treat-ment for children with intractable epilepsy.

View full abstract

Flunarizine is of established value for the treatment of cerebral circulatory disorders such as vertigo and migraine. Moreover, flunarizine shows antiepileptic effects. We stndied this antiepileptic effects in 15 children with intractable partial epilepsy. They were between 6 and 16 years of age (mean 10. 9 years old), and their seizures repeated weekly or daily in spite of the therapeutic plasma level of standard antiepileptic drugs. Flunarizine was given in a dosage from 5 mg to 10 mg daily, and comedication remained unchanged throughout.
Eight of 15 patients (53%) showed an improvement. One patient showed a 75% reduction of seizure incidence, 7 more than 50% and 7 unchanged. But two of them improved only transiently, suggesting the development of tolerance to the drug. Adverse effects of sleepiness and increasing appetite manifested in 8 patients, but were not severe. The plasma levels of comedication anticonvulsants were not influenced to flunarizine therapy. One patient, who were examined regional cerebral blood flow using IMPSPECT before and during flunarizine therapy, showed improvement of regional cerebral blood flow in epileptic foci. This suggested that the effect to cerebral circulation might be related to the mechanisms of flunarizine antiepileptic properties.

View full abstract

In childhood partial epilepsies, intcrictal focal seizure discharges present in the waking EEG occasionally show a significant increase throughout all stages of sleep. The spikes may spread during slow wave sleep to the adjacent regions, and, in some cases, may display significant bilateral diffusion. We studied EEG changes, evolution of seizures, changes of mental functions, and prognosis in 25 patients whose EEGs demonstrated such generalization similar to the continuous spike-wave sleep (CSWS) syndrome. The ages of patients at follow-up ranged from 8 to 19 years. Patients were divided into 3 groups as follows; group 1: 11 patients with only EEG generalization, group 2: 10 patients with non-convulsive generalized seizures, and group 3: 4 patients with significant psychomotor deterioration.
The results were as follows;(1) group 1 patients were the oldest at the time of generalization of focal seizure discharges and showed spike-wave indexes of less than 85% in non-REM sleep, (2) group 2 patients with non-convulsive generalized seizures had more focal motor seizures and speech problems with localization of focal seizure discharges on central areas, (3) all group 3 patients with psychomotor deteriorations showed spike-wave indexes of more than 85% in non-REM sleep, (4) when EEGs were normalized, prognosis was relatively good.
We considered that a variety of symptoms during a period of a generalization of focal seizure discharges was related to a localization of focal seizure discharges and a continuity of generalized spike-waves. And we should pay attention to mild psychic symptoms, such as, personality changes or abnormal behaviors during the period of generalization of focal seizure discharges even if spike-wave indexes in non-REM sleep were less than 85%.

View full abstract

KW 6066 N is a sustained release preparation of valproic acid (VPA) intended to prolong the rate of bioavailability by delaying the absorption velocity. Theoretically, the use of this preparation permits the patients to reduce the number of times of drug intake a day because the daily fluctuation of serum level in steady state becomes small.
The authors could confirm good results by using this drug once a day after supper in 20 patients (10 cases with functional partial epilepsy and 10 with primary generalized epilepsy of which mean ages are 10 and 15 years, respectively). Their seizures had been entirely suppressed for more than six months by VPA therapy (VPA alone in 18 and in combination with carbamazepine in 2). After obtaining informed written consent of these patients or their families, VPA given hitherto was replaced by the same dose of KW 6066 N. The drugs were taken once a day after supper with the combined drugs, if any, and the clinical courses for more than 12 months were observed.
Eighteen patients (90%) showed complete suppression of seizures until the end of observation periods. After shifting to KW 6066 N, there were neither patients who developed new side-effects nor cases that required the discontinuation of once daily administration.
Mean level dose ratio (μg/ml/mg/kg) of KW 6066 N monitored early morning before drug intake was significantly higher than that of VPA (4.0±1.4 in KW6066N and 2.5±0.9 in VPA, respectively). Accordingly, slow releasing effect of KW6066N was confirmed.

View full abstract

The efficacy of zonisamide, a new antiepileptic drug, was studied in 36 children with refractory epilepsy. The mean age of these patients was 13 years and two months. Zonisamide was administered as add-on treatment to the preexisting anticonvulsant regi-men. The average follow up period was 9.5±7.5 months. Seizure frequency significantly reduced in 8 patients (22%), of whom 3 experienced greater than 75% reduction and 5 a 50-75% reduction in seizure frequency. Analyzing the results according to seizure types, improvement in seizure control was observed in 6 of 24 patients (25%) with partial seizures, and 2 of 3 patients with generalized tonic clonic seizures. Addition of zonisamide had no effect on tonic, myoclonic, atypical absence or atonic seizures. The mean dosage and serum anticonvulsant concentration were 7.8±4.6 mg/kg, and 24.8±9.2μg/ml, respectively in effective cases. Side effects were observed in 21 (58%) of 36 cases. These were most commonly drowsiness, loss of appetite, and mild mental slowing. Two patients developed a transient psychosis. All side effects disappeared after a decrease in dosage or on withdrawal of zonisamide.

View full abstract

Evolutional process from the West syndrome into the Lennox-Gastaut syndrome was studied clinico-electroencephalographically on 30 cases who underwent the evolution from the West syndrome into the Lennox-Gastaut syndrome.
1) Both disappearance of tonic spasms in series and appearance of single tonic spasms were most often observed between six months and one year of age.
2) Hypsarythmia disappeared mainly between six months and one year of age, being followed by the appearance of diffuse slow spike-and-waves at between one and two years of ages.
3) Time of evolution from the West into the Lennox-Gastaut syndromes concentrated on ages betweeen one and three years. The transitional process developed gradually during several months.
4) The Lennox-Gastaut syndrome evolved from the West syndrome was characteristic in both clinical seizure patterns and its very poor prognosis.
These findings suggested the importance of clinical efforts to prevent evolution from the West to the Lennox-Gastaut syndromes.

View full abstract

Clinical and electroencephalographic features of myoclonic seizures (MS) were studied in 149 patients. On the basis of early development history, age at onset of epilepsy, combination of tonic spasm (TS), and an existence of generalized bilateral synchronous slow spike and wave burst (GSSW) or multifocal spikes (MFS) in interictal EEG, the patients could be placed into 5 groups:
Group A (60 cases): Normal prior development to onset of epilepsy, absence of TS, GSSW and MFS. This group showed a high incidence of either febrile convulsions or epilepsy in the family history (FH), and MS being predominant seizure type. Prognosis for seizure control and mental outcome ranged from fair to good. Group B (18 cases): Normal prior development, presence of TS, GSSW. Seizure and mental outcome was poor. Group C (13 cases): Normal prior development, absence of TS, GSSW, and the combination of MFS and the age of onset less than 1 year. This group also exhibited a high incidence of FH and multiple seizure types, easily precipitated by fever. Prognosis was very poor. Group D (17 cases): Delayed development with gross neurological abnormalities often associated cerebral palsy. Group E (29 cases): Delayed development before onset of seizures and history of West syndrome without gross neurological abnormalities in all patients. The remaining 12 patients could not be classified.

View full abstract

We studied clinical and EEG features of 60 patients with idiopathic ME in infancy and early childhood with benign prognosis. They showed normal development before onset and a high incidence of either febrile convulsions or epilepsy in the family history (36%). The mean age of onset of myoclonic seizures (MS) was 30±13 months. In addition to MS, the patients often exhibited generalized tonic clonic seizurees (70%), myoclonic astatic or astatic seizures (64%), atypical absence (53%), minor epileptic status (20%) and nocturnal generalized seizures (NGS)(63%). Early in the evolution, frequency of the seizures increased and they became resistant to medical therapy. However, the long-term seizure prognosis ranged from fair to good. All patients entered remission within several years. The final intellectual outcome ranged from normal to mildly retarded. The patients could be placed into 3 subgroups according to the frequency of NGS: goup A 1 (without NGS), A 2 (rare NGS), A 3 (frequent NGS). Although much better prognosis in the seizure and intellectual outcome correlated inversely with the frequency of NGS, they form a continum. These findings lead us to conclude that idiopathic ME in infancy and early childhood is an epileptic syndrome with a relatively wide spectrum concerning the prognosis of the patient's seizures and intellectual development.

View full abstract

Blood ammonia levels were examined in 300 patients (range: 0-24 years old) receiving antiepileptic drugs (AEDs). Hyperammonia (ammonia level over than 86.0 μg/ml/ by enzymatic method) was found in 66 cases (22.0%), 33 males and 33 females. As 65 out of 66 hyperammonemic patients on AED were given VPA and their blood ammonia levels returned to normal after VPA withdrawal, almost hyperammonemia on AED might be induced by VPA. he mean serum VPA levels in patients with hyperammonemia was 66.7±22.5μg/ml, but there was no relationships between serum VPA levels and blood ammonia levels of patients with hyperammonemia. The maximum ammonia level (446.3μg/ml) was found in multiply handicapped 13 years old girl who was sufferring from erythema infectiosum followed by acute evidence of repetitive convulsions and lethargy. After withdrawal of VPA, convulsions were controlled within a day, and also her physical and conscious state recovered to the former level within 2 days. Alternations in the state of consciusness, increased epileptic seizures, poor activity and vomiting were main manifes-tations of patients with hyperammonemia. Comparision of motor function of 65 hyperammonemic patients with that of 129 normoammonemic patients on VPA showed that diminished daily activity had probably promoted hyperammonemia. The mean number of AED in hyperammonemic patients was 3.4±11.2 and in normoammonemic patients was 2.3±1.0. In 15 patients with hyperammonemia, there was previous symptoms that was highly suggestive of respiratory truct infection. In conclusion, almost hyperammonemia on AED might be induced by VPA and polypharmacy, respiratory truct infections, lack of daily activity and malnutrition pro-bably trigger hyperammonemia. We recommended regular check of blood ammonia levels in patient receiving VPA. And also we recommended emergency check of bloo ammonia level when we foud out the symptoms after increasing of VPA.

View full abstract

We report seven cases of intractable childhood epilepsy with generalized tonic-clonic seizure.
The following six are the clinical characteristics of the seven cases described in this report:
(1) A child who did not have any presumed disorders, and was generally under normal development.
(2) Develops initial seizures before the age of one year.
(3)The seizure type during the initial stage in infancy would mainly be either unilateral, or generalized clonic seizure, or generalized tonic-clonic seizure. When the childhood is reached, the generalized tonic-clonic seizures are repeated and later, they develop remarkable therapy resistance.
(4) During the course of development, there are some cases who also show another seizure type that may possibly be complex partial seizures, but they are short-lived.
(5) It is not distinct at the onset, but as the patient grows older, the mental retardation becomes clearer gradually.
(6) The EEGs initially lack epileptic discharges, and later they will show generalized spike-and-wave, or generalized polyspike-and-wave complexes. However, the rate of occurrence of those is relatively low despite the frequent occurrence of the clinical seizures.
The epilepsy thus categorized cannot be regarded as an epileptic syndrome, but since it is intractable, further study is necessary for disclosing its cause and, therefore treatment.

View full abstract

The authors studied the relation of early response to antiepileptic therapy, which was evaluated at 2 years after the beginning of the therapy, to the long-term prognosis of seizure, in 89 cases under observation for 10 to 15 years, and found a significant correlation between the early response and prognosis. Namely, when seizure showed good response to AED in 2 years after the beginning of the therapy, it tended to lead to favorable prognosis, and vice versa. However, the correlation appeared to be influenced by some clinical factors in epilepsy: seizure type, etiology, neuro-psychiatric complications, and so on. Accordingly, we analyzed the factors and revealed that good response to early treatment and favorable prognosis were strongly linked in the cases without organic etiology and those of onset below 10 years of age. On the other hand, poor response to early treatment highly related to the unfavorable prognosis in the cases with partial seizures, those with neuro-psychiatric complications and those of onset below 10 years of age.

View full abstract