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Vitamin B(6) (VB(6))-related seizures include clinical seizures associated with VB(6) deficiency and dependency. Both types of seizures are suppressed by VB(6). We proposed VB(6)-responsive seizures as the third category of VB(6)-related seizures in 1977. Vitamin B(6)-responsive seizures decrease or disappear in response to high-dose oral VB(6). Seizure onset in most of our cases occurred within the first year of life, although this varied between 3 months and 5 years. Etiologically, such cases were not only idiopathic or cryptogenic, but also symptomatic and associated with organic brain lesions. The tryptophan load test was usually negative. Vitamin VB(6)-responsive seizures or epilepsy were usually West syndrome (WS), however may also include Lennox-Gastaut syndrome, grand mal or partial motor seizures. High-dose VB(6) treatment administered to 216 consecutive WS cases had an overall response rate of 13.9%, being high not only in cryptogenic cases (32%), but also in symptomatic WS (11.5%) associated with identifiable brain pathologies. Notably, responsive patients had excellent long-term seizure and mental outcomes without the need for conventional antiepileptic medication. A gradual increase in clinical response to VB(6) was noted with increasing the VB(6) dose from 30 to 50-100mg/day, and a dramatic increase in clinical response with high-dose VB(6) (100-400mg). Little clinical response was noted with administration of low dose VB(6) (10-30 mg/day). Thus, high-dose oral VB(6) treatment is recommended in all WS patients at time of initial treatment for a minimum of 10 days, considering the safety and rapid onset of efficacy, usually within 1 week, of this treatment.

ラモトリギン(LTG）の小児難治てんかんに対する効果を検討するため、ゾニサミド(ZNS）を対照とする単盲検法で、LTGまたはZNSを12週間、既存の抗てんかん薬に付加投与し、有効性と有用性を168例、安全性を169例で比較解析した。最終全般改善率はLTG群44%、ZNS群24%で、LTGのZNSに対する非劣性が検証された。Lennox-Gastaut症候群の全般発作に対するLTGの発作半減効果は39%で、ZNS群の13%に比し有意に高かった。有害事象発現率は、LTG群43%、ZNS群54%で、両群ともに傾眠が多かった。因果関係が疑われた重篤な副作用は、LTG群のてんかん発作増悪とStevens-Johnson症候群の各1例であった。LTG群の48%、ZNS群の39%が「安全」と評価されたが、有意差はなかった。LTG群の38%、ZNS群の22%が有効性と安全性を総合して「有用」と判定され、LTG群で有意に高く(p=0.0287）、LGSを含む小児の難治てんかん治療におけるLTGの意義が明らかになった。

Background Markand and Blume first realized the specificity of the EEG pattern of multiple independent spike foci (MISF) in the late 1970s; its close relation with hypsarrhythmia and slow spike-waves, extensive bilateral brain lesion, and intractable seizures. But they did not recognize it as an epileptic syndrome. On the other hand, the authors had been taken notice of severe epilepsy with MISF (SE-MISF) as a peculiar clinico-electrical entity showing “generalized seizures”, and pointed out its close relation to Lennox–Gastaut syndrome (LGS) from the long-term follow-up of LGS. Summary points SE-MISF is characterized by (1) interictal EEG showing multiple independent spike foci (three or more foci in both hemisphere, i.e. at least one in each hemisphere) and diffuse slowing of the background activity. Diffuse epileptic discharges are rare. (2) The main seizure type is frequent generalized minor seizures, often tonic spasms. (3) Mutual transition is often observed between the age-dependent epileptic encephalopathies, i.e. Ohtahara syndrome, West syndrome and LGS. (4) The age at epilepsy onset is early, but the onset of SE-MISF is variable. (5) It is often associated with mental retardation and neurological abnormalities, usually severe. (6) Etiology is variable and largely nonspecific, including prenatal, perinatal, and postnatal cerebral pathologies. (7) Prognoses for seizures and psychomotor development are poor. Seizures are very intractable and may cause psychomotor deterioration. Conclusion SE-MISF may be classified into symptomatic generalized epilepsy, namely a diffuse encephalopathy with mutual transition between other age-dependent epileptic encephalopathies. This characteristic entity may be acknowledged as a new epileptic syndrome.

Zonisamide safety was evaluated based on a postmarketing surveillance study of patients treated for 1–3 years. Nine hundred twenty-eight children and 584 adults (ages 1 month to 79 years), including 372 newly-diagnosed patients, received zonisamide for partial and generalized epilepsies. Of the intractable patients, 1008 received zonisamide in combination with other antiepileptic drugs (AED), and 52 successfully transitioned to zonisamide monotherapy. A total of 1089 adverse events occurred in 476 (31.5%) of 1512 patients. Incidence of adverse effects was significantly lower among patients receiving zonisamide monotherapy than in those receiving polytherapy: 21% (18.9% of children, 29.4% of adults) versus 35.6% (30.4% of children, 41.7% of adults), respectively. The total incidence of adverse effects was lower for children (26.2%) than for adults (39.9%). Most common adverse events included mental/psychiatric symptoms (19.4%), gastrointestinal symptoms (8.7%), and neurological symptoms (5.8%). Effects that seemed unique to zonisamide were impairment of mental function, motivation or volition, and hypohidrosis. Urinary calculi were detected in only two patients (0.13%). Teratogenicity was evaluated in six patients. Two patients on zonisamide monotherapy and three on polytherapy delivered normal children. One of four patients on polytherapy conceived a fetus with a skull defect with cerebral and cerebellar dysgenesis.

The effect of lactation on the pharmacokinetics of phenobarbital (PB) after delivery was studied in female rats. Non-pregnant animals received PB 20 mg/kg/day twice for 6–7 days before mating, during pregnancy and after delivery. Chronic PB did not significantly influence changes in the body weight of rats after delivery. On the first post-delivery day, the plasma PB concentration in the PB-treated rats was significantly higher than that in PB-treated, non-pregnant rats (non-pregnant rats); and thereafter, it gradually decreased until ablactation on the 20th day. After ablactation, plasma PB concentrations gradually returned to the level before delivery. In PB-treated rats, pharmacokinetic parameters (Cmax, AUC0–12) of PB between 0 and 12 hr after a single oral administration were significantly decreased during lactation. These results suggest that PB administered during lactation is transferred in part to offspring through maternal milk.

The phenobarbital (PB) transition from epiletpic mothers to their breast milks and offspring in cases of PB monopharmacy with other antiepileptic drugs was investigated in 26 epileptic mothers and 24 offspring who were taking the breast milk from epileptic mothers. The mother's serum PB concentration in monopharmacy was almost the same in various stages (stage I, with 5 days after the delivery; stage II, 6--10 days after; stage III, 1--2 mothers after; stage IV, 3--5 months after). However, the PB concentrations in polypharmacy were markedly higher than those in monopharmacy. Concerning the PB concentration in breast milk, a significant increase was found in polypharmacy in comparison with monopharmacy only in stage I. On the other hand, the offspring's PB concentration in polypharmacy was markedly higher than that in monopharmacy, particularly in stage I. In another stages, PB concentration in monopharmacy gradually decreased according to the increase of stages. These results indicate that pharmacokinetics of antiepileptic drugs in the perinatal may be considerably different in PB monopharmacy and polypharmacy.

A simple and rapid method for the quantitation of concentrations of lamotrigine, a novel antiepileptic, in human serum was developed with high-performance liquid chromatography, using a solid-phase extraction technique. The mobile phase was composed of acetonitrile-10 mM phosphate buffer (pH 3.5) containing 5 mM sodium octanesulphonate (27:73, v/v), and components were detected at 265 nm. Retention times of acetanilide as an internal standard and lamotrigine were 3.4 and 10.3 min, respectively. The coefficients of variation were 3.1-4.5% and 4.4-9.8% for the within-day and between-day precision estimates, respectively. The extraction recovery of lamotrigine added to blank serum was 86-107%. The quantitation limit of lamotrigine was ca. 0.2 microgram/ml in 100 microliters of serum. These results suggest that the method employed in this study is useful for the routine monitoring of serum concentrations of lamotrigine in epileptic patients.

We investigated the etiology of West syndrome (WS) with special reference to prenatal factors in 180 cases. Prenatal cause was the most frequent diagnosis (77 cases, 42.8%), followed by perinatal (25 cases, 13.9%) and postnatal factors (12 cases, 6.7%); 48 cases (26.7%) were of uncertain etiology; eighteen cases (10.0%) were idiopathic. Of the three forms of age-dependent epileptic encephalopathy, prenatal cause was present in 12 of 15 cases (80.0%) of early-infantile epileptic encephalopathy with suppression-burst, 77 of 180 cases (42.8%) of WS, and 31 of 123 cases (25.2%) of Lennox-Gastaut syndrome (LGS). Prenatal factors of WS included tuberous sclerosis (23), chromosome abnormalities (10), cerebral dysgenesis (10), porencephaly (7), hydrocephalus (5), Aicardi syndrome (3), Aicardi syndrome associated with chromosome abnormality (1), and other causes (18). Chromosome abnormalities with WS consisted of 6 cases with 21 trisomy and one case each with 18q duplication, t(1;y) translocation, 7q duplication, and partial 2p trisomy. One patient with Aicardi syndrome also had a t(12;21) translocation. No significant difference was observed in the age of onset of WS among the five etiologic groups. The evolution from WS to LGS was not influenced by etiology, except for the idiopathic group. In patients followed for over 3 years, seizure remission occurred in 46.8% (22 of 47 cases) of the prenatal group. This was lower than the other four groups. Intellectual prognosis was also relatively poor in those with prenatal onset. Pyridoxal phosphate (PAL-P) treatment was effective in 9 of 70 (12.9%) prenatal cases and 5 of 18 (27.8%) idiopathic cases.(ABSTRACT TRUNCATED AT 250 WORDS)

This paper reviews findings and problems concerning EEG in febrile convulsions, and outlines our classification and pathophysiological concepts.Prospective studies have almost negated the prognostic value of EEG on recurrence of febrile convulsions and subsequent afebrile seizures. A particular problem is the low detection rate of epileptic discharges before age 3, i.e. preferential onset age of febrile convulsions. Repeated and long-term follow-up EEG studies, however, enhance its prognostic value. EEG findings and clinical risk factors have to be considered in the prognostication of febrile convulsions. To clarify this point, long-term systematic follow-up study should be extended beyond adolescence.

SummaryZonisamide safety was evaluated based on a postmarketing surveillance study of patients treated for 1–3 years. Nine hundred twenty-eight children and 584 adults (ages 1 month to 79 years), including 372 newly-diagnosed patients, received zonisamide for partial and generalized epilepsies. Of the intractable patients, 1088 received zonisamide in combination with other antiepileptic drugs (AED), and 52 successfully transitioned to zonisamide monotherapy. A total of 1089 adverse events occurred in 476 (31.5%) of 1512 patients. Incidence of adverse effects was significantly lower among patients receiving zonisamide monotherapy than in those receiving polytherapy: 21% (18.9% of children, 29.4% of adults) versus 35.6% (30.4% of children, 41.7% of adults), respectively. The total incidence of adverse effects was lower for children (26.2%) than for adults (39.9%). Most common adverse events included mental/psychiatric symptoms (19.4%), gastrointestinal symptoms (8.7%), and neurological symptoms (6.5%). Effects that seemed unique to zonisamide were impairment of mental function, motivation or volition, and hypohidrosis. Urinary calculi were detected in only two patients (0.13%). Teratogenicity was evaluated in six patients. Two patients on zonisamide monotherapy and three on polytherapy delivered normal children. One of four patients on polytherapy conceived a fetus with a skull defect with cerebral and cerebellar dysgenesis, namely anencephaly.

Ohtahara syndrome (OS) is well known as a peculiar early onset epileptic syndrome with serious prognosis. The outline of OS, mainly in relation to the evolution with age, and differentiation from related conditions, particularly early myoclonic encephalopathy (EME) were mentioned. Results Etiologically, structural brain lesions are most probable in OS, and non-structural/metabolic disorders in EME. Clinically, tonic spasms are the main seizures in OS, while myoclonia and frequent partial motor seizures in EME. Another difference is noted in EEG findings: suppression-bursts (SB) are consistently observed in both waking and sleeping states in OS, but suppression-bursts become more apparent in sleep in EME. The course observation clarifies differences between both syndromes; SBs evolve to hypsarrhythmia around 3–4 months of age, and sometimes further to diffuse slow spike-waves in OS. In contrast, in EME suppression-bursts may persist up to late childhood after a transient evolution to hypsarryhtmia in the middle to late infancy. Transition between syndromes is also specific; OS evolves to West syndrome, and further to Lennox–Gastaut syndrome with age, but EME persists long without such evolution excepting a transient phase of West syndrome. Conclusion These clinicoelectrical characteristics and differential points strongly indicate the efficiency of the developmental study to delineate both syndromes

For the successful treatment of epilepsy, accurate diagnosis of epilepsy and epileptic seizures, and proper selection of antiepileptic drugs (AED) according to the classification of epileptic syndromes are fundamentally important. Efficacy of AED treatment, however, depends not only on its pharmacological action but also on its efficient use, namely a rationally thinking tailor-made treatment considering the characteristics of each patients, i.e. individual differences in pharmacokinetics, factors influencing AED concentrations, AED interactions, and comprehensively their life style and psychosocial factors.

Early infantile epileptic encephalopathy with suppression-burst, or Ohtahara syndrome (OS), and early myoclonic encephalopathy (EME) are epileptic encephalopathies with onset of frequent seizures in the neonatal and early infancy period and with a characteristic EEG pattern, namely, suppression-burst, in which higher-voltage bursts of slow waves mixed with multifocal spikes alternate with isoelectric suppression phase. Their nosologic independence is now widely accepted, although some controversy initially occurred because of their common characteristics such as age of onset, EEG features, seizure intractability, and poor prognosis. Major differences between the two syndromes include (1) tonic spasms in OS versus partial seizures and erratic myoclonias in EME, (2) continuous suppression-burst pattern in both waking and sleeping states in OS versus this EEG pattern almost limited to sleep in EME, and (3) static structural brain damage in OS versus genetic or metabolic disorders in EME. The most important differentiating point is their evolutional pattern with age, which may reflect their pathophysiologic difference. Ohtahara syndrome evolves to West syndrome and further to Lennox-Gastaut syndrome with age, but EME demonstrates no unique evolution; namely, it continues as such for a long time or changes into partial epilepsy or severe epilepsy with multiple independent spike foci.

Severe epilepsy with multiple independent spike foci is an electroclinical entity with the following characteristics: (1) EEG showing multiple independent spike foci (three or more foci in both hemisphere, i.e., at least one in each hemisphere) and diffuse slowing of the background activity, (2) very frequent multiple types of seizures but mainly generalized minor seizures, (3) frequent association with mental retardation and neurologic abnormalities, (4) underlying causes of various nonspecific prenatal, perinatal, and postnatal cerebral conditions, and (5) poor prognoses for seizures and psychomotor development. It represents a diffuse encephalopathy with mutual transition between other age-dependent epileptic encephalopathies. This electroclinical condition may be appropriately named Markand-Blume-Ohtahara syndrome, after Markand and Blume, who initially described in detail the EEG pattern of multifocal spike discharges with its major clinical correlates, and Ohtahara, who extensively studied the group of patients with both clinical and EEG characteristics and proposed the concept of severe epilepsy with multiple independent spike foci, classifying it as one type of generalized epilepsy.

The goal of this study is to clarify the prognostic factors in childhood localization-related epilepsy in a tertiary medical center. Children (n = 113) with symptomatic and cryptogenic localization-related epilepsy were divided into groups of intractable patients (average seizure frequency: one or more per month during the 6 months before the last follow-up; n = 40) and well-controlled patients (no seizures for at least 1 year before the last follow-up; n = 73). Clinical and electroencephalogram (EEG) factors were examined to elucidate prognostic factors. The subtypes of epilepsies and causes were also investigated. Univariate analyses indicated that the following factors were correlated with seizure outcome: (1) seizure type at the first visit; (2) seizure frequency; (3) underlying cause; (4) age at onset of epilepsy; (5) status epilepticus occurring as the first seizure and before the first visit; and (6) diffuse epileptic discharges on first visit interictal EEGs. Multivariate analyses revealed that seizure type at the first visit, seizure frequency, status epilepticus before the first visit, and underlying causes were significant independent predictive factors. The rate of intractable patients was highest in multilobar epilepsy, followed by frontal-lobe epilepsy. Regarding etiologies, the intractable group contained nine patients with encephalitis of unknown origin and three each with localized cortical malformation and mesial temporal sclerosis.

116 immunizations were given to 61 children with febrile convulsion or epilepsy who had not had a seizure for 1 year since the last attack. In 92 of the 116 immunizations the electroencephalogram (EEG) was examined before and after immunization. No adverse effects on the EEG were observed in 19 immunizations with Japanese encephalitis, measles, mumps or rubella vaccines. Epileptic spikes reappeared after 10 immunizations and epileptic spikes increased after 10 immunizations among 73 given for diphtheria, acellular pertussis and tetanus (DPT), diphtheria and tetanus (DT), or Bacillus Calmette-Guerin (BCG). A convulsion was observed once in one child 7 days after immunization with BCG. A follow-up EEG examination is necessary after children with convulsive disorders are immunized.

A clinico-electroencephalographic study on 14 cases of the early-infantile epileptic encephalopathy with suppression-burst (EIEE) including long-term follow-up studies for one year 8 months to 12 years 2 months disclosed the specificity of EIEE in its developmental aspects. With age, clinical evolution from EIEE to the West syndrome was observed in as many as 10 cases, among which two cases showed further transition to the Lennox-Gastaut syndrome. Electroencephalographically, suppression-burst pattern gradually began to disappear from age of 3 months and disappeared by 6 months in all the cases, transforming to hypsarhythmia in 10 cases from 2 to 6 months of age, showing further transition to diffuse slow spike-and-waves in 2 cases at one year and one month and at 3 years and one month of age, respectively. Changing pattern of EEG were classifiable into two types which strongly related to the prognosis. These findings indicated EIEE to be an independent epileptic syndrome as the earliest form of the age-dependent epileptic encephalopathy.

従来記載されていない特異なnon-convulsive status epilepticusの1型について報告した。これは意識障害を伴わない短い脱力のエピソードの頻発を主徴とし, 脳波ではエピソードの頻発期には覚醒時は焦点性ながら広汎化する棘徐波複合が頻発するが, 上記のエピソードはこれと時間的に厳密な相関を示さず, てんかん発作そのものとは考え難かった。睡眠時には広汎性棘徐波複合が連続する特異なパターンを示し, この点ではsubclinical electrical status epilepticus induced by sleep (ESES) に類似していた。寛解期には焦点性発射が主となり上記のパターンは睡眠中にも見られなかった。なお頻発期に精神神経症状を示すことも注目された。以上によりこれら症例群はESESに近縁ながら別個の病態と考えられた。

The electro-clinical characteristics of childhood epilepsy are known to appear during the development of the brain and to change their features with age. Accordingly, developmental viewpoints are indispensable to researches on childhood epilepsy. Age-dependent epileptic encephalopathy has the most remarkable developmental characteristics among childhood epilepsies. Early-infantile epileptic encephalopathy with suppression-burst (EIEE), the West syndrome and the Lennox-Gastaut syndrome, which constitute age-dependent epileptic encephalopathy, have many common features. Each of these three syndromes, however, has its own distinctive clinical and electro-encephalographic specificities, and shows mutual transition with age. Results of developmental studies on the West syndrome are described, confirming it as one type of age-dependent epileptic encephalopathy. 1) On the basis of the long-term follow-up study of 14 cases of EIEE, sequential transition from EIEE to the West, and further to the Lennox-Gastaut syndrome was observed, with reference to critical changing period, transitional patterns and prognoses. 2) Analytical follow-up study of 83 cases of the West syndrome, divided into idiopathic and symptomatic groups showed its evolution into the Lennox-Gastaut syndrome to be important for its prognosis, with reference to the various factors relating to this transition.

The process of discontinuing anticonvulsant therapy was studied clinicoelectroencephalographically on 285 children with epilepsy. The subjects were divided into two groups electroencephalographically: First, 190 cases of the formally discontinued group which had antiepiletic drugs withdrawn after the cessation of clinical seizures and suppressing epileptic discharges for over two years and, second, 95 cases which were informally discontinued. The relapse rate after discontinuation was significantly lower in the former group, 2.1%, than the latter group, 21.1%. Concerning the seizure-free period, among the cases free from clinical seizures for over three years at the time of withdrawal, the relapse rate was significantly lower than the rest of the cases. Moreover, the spike-free period proved to be a more reliable indicator for stopping medication than the seizure-free period. From these findings, the withdrawal of antiepileptic drugs should be started after suppression of epileptic discharges for over two years in childhood epilepsy.

The long-term clinical and electroencephalographic follow-up studies were carried out for more than three years, up to 14 years in the longest, on 116 cases with Lennox syndrome. And the results of s-ystematic study on changing patterns and out come have been reported. The follow-up examination was performed also on West syndrome which is closely related with Lennox syndrome; especially the relationship between both syndromes regarding prognosis has been clarified. (1) According to the long-term follow-up on 116 cases with Lennox syndrome, there were 98 cases (84.5%) having mes (61.2%) and persisted as Lennox syndrome except for one case. (2) Generally speaking, the cases with age of onset before two years old showed unfavorable outcome. (3) There were 42 cases (36.2%), which were converted from West syndrome and showed markedly unfaborable prognosis in regard to intelligence as well as the remainging of seizure. (31 cases, 77.5%) (4) On thehand, in 23 idiopathic cases, which showed no developmental retardation before onset of seizure, had favorable outcome, and the remaining of seizure was observed in eight cases (34.8%). However, even in such cases, it was noticed that those displaying mental defect at the follow-up attained 14 cases (60.9%). That is to say, it was clarified that persistence of even minor seizures induced mental deterioration. (5) The cases with favorable prognosis showed usually a typical slow spike-and-wave pattern electroencephalographically, whereas those with poor prognosis showed mostly an asymmetric or disorganized slow spike-and-wave pattern. (6) In many cases displaying signs of brain atrophy with pneumoencephalograpm and accompanying overt neurological signs at the initial examination, prognosis is obviously poor. (7) From the follow-up examination on 94 cases with West syndrome for three to 15 years transformed into Lennox syndrome Among them, those cases with the remaining of seizure at the time of follow-up were 44 (46.8%) out 94 cases, of which 37 cases (83.8%) had remaining seizure as Lennox syndrome. (8) From the above results, it is emphasized that Lennox and West syndromes show close relationship with each other and that a study should be done on the interrelation between their prognosis.

This report deals with a 1.5-year-old male infant terminating in viral pneumonia and "diabetes insipidus". The autopsy revealed malignant pituitary chromophobe adenoma, invading the wall of the third ventricle, extending to the periventricular-, dorsomedial- and ventromedial area, skipping to the lateral area adjacent to the optic nerve, and permeating into the subarachnoid space of the cerebrum. At the onset of disease polydypsia and polyuria were marked followed by interstitial pneumonia with high fever, and later generalized tonic convulsion terminated in death. This case is peculiar in at least two respects. Firstly, this is the youngest reported case of malignant chromophobe adenoma. Secondly, the manifestation of diabetes insipidus is rare in chromophobe adenoma. The malignant adenoma probably occurred from the primitive gland rest of chromophobe cells in the posterior lobe becoming malignant during the course of growth development and destroyed the cells of the posterior lobe, resulting in diabetes insipidus.

To investigate the significance of EEG findings relating to the appearance of psychic symptoms in epileptic children, a clinicoelectroen-cephalographic study was undertaken on 15 cases with psychotic episodes. 1) Psychotic episodes with hallucination and/or illusion were observed, though rarely, in childhood epilepsy. These seemed liable to occur in temporal lobe epilepsy. 2) Three of four patients in the hallucination and illusion group showed frequent epileptic discharges. However, no distinct relation existed between seizure discharges and psychotic episodes. 3) Eight of 11 patients in the dysphoria and excitement group were secondary generalized epilepsy. 4) In the dysphoria and excitement group, psychotic episodes occurred either as a result of the increase in epileptic discharges or conversely as a result of the suppression of epileptic discharges. The former was more frequent. Epileptic discharges tended to be suppressed in the Lennox syndrome and allied conditions relating to psychotic episodes. 5) A forced normalization-like phenomenon mostly resulted from the marked suppression of diffuse slow spike-waves. However, a complete suppression of epileptic discharges was not always noted.

Remarkable progress has been accomplished in epileptology in recent years. The remission rate in childhood epilepsy has been improved by the introduction of new technologies and better diagnostic as well as therapeutic methods. Investigation of prognosis is an important field of epileptology, because prognostic improvement reflects its overall progress. A long-term follow-up study of childhood epilepsy was undertaken in the Okayama University Hospital. Ten to 15 years of follow-up was possible in 730 of 1,295 patients who were first diagnosed at ages below 15 years, from 1968 to 1971. The 3-year remission rate amounted to 82.0% and 5-year remission was obtained in 79.1%. These high rates of remission indicate the favorable prognosis of childhood epilepsy. On the other hand, cases of intractable epilepsy also amounted to a considerable number. Intractable epilepsy consisted mainly of age-dependent epileptic encephalopathy (Ohtahara's syndrome, West syndrome and Lennox-Gastaut syndrome) and severe myoclonic epilepsy in infancy. Development of effective therapy for these intractable epileptic syndromes will be an important subject of future studies.

A boy, who started remittent fever reaching 40°C at the age of 4 years and 9 months and gradually developed hepatosplenomegaly, lymphadenopathy, pancytopenia, and hypergammaglobulinemia, is reported. Aspirated bone marrows contained sea-blue histiocytes, and nitroblue tetrazolium test was abnormal. X-ray examination revealed a tumor mass in the right lung, uremia occurred terminally, and he died at the age of 10 years and 3 months. Surgical specimens, obtained by splenectomy, and necropsy revealed the presence of characteristic sea-blue cells in the bone marrow, spleen, lymph nodes, liver, and kidneys, and pseudotuberculous granulomas with or without aspergillus in the lungs, epicardium, liver, and lymph nodes. Histochemically, sea-blue granules accumulating in the cytoplasm of the histiocytes were proved to be a lipogenic ceroid-like pigment. Electron microscopically, these granules were comprised of round or ovoid, membrane-bound or free lipid droplets of various sizes and electron densities, occasionally containing poorly oriented, lamellar structures. The nature and possible pathogenesis of the sea-blue histiocytosis in this case are discussed briefly. ACTA PATHOL. JPN. 34 : 1385–1401, 1984.

In 45 cases of Lennox syndrome treated with ACTH, the immediate and long-term effects and the various factors affecting them were investigated by a follow-up study. 1) Regarding the immediate effect, 23 (51.1%) of the 45 cases became "seizure free" for over 10 days. 2) As to the long-term prognosis of these 23 cases, 10 cases relapsed into Lennox syndrome within 6 months and in the remaining 13 cases, seizures were suppressed for over 6 months; out of these 13, seizure relapse was observed in eight cases from 9 months to 7 years later, and the other five cases followed a very favorable course without relapse. 3) The favorable factors related to the effect of ACTH for Lennox syndrome are: a) age at ACTH treatment: up to 4 years old, b) time lag between onset of Lennox syndrome and initiation of ACTH treatment: the shorter the better; at least within 1 year, preferably within 3 months, c) presumptive causes and underlying diseases: idiopathic cases are best, d) mental defects before treatment: the slighter the better, e) seizure patterns: without tonic seizures, and f) EEG findings: disorganized diffuse slow spike-waves without asymmetry. 4) It is desirable to continue the ACTH treatment as long as possible, with the goal of the disappearance of seizure discharges, or at least the disappearance of diffuse seizure discharges.

A multifaceted study on childhood refractory epilepsy disclosed an insufficient classification of epilepsies and epileptic seizures, and inappropriate polypharmacy as the most important factors preventing appropriate therapy. By means of an adjustment of AEDs based on the accurate classification of epilepsies and epileptic seizures, the number of AEDs could be reduced in 37.5% and monotherapy was successful in 13.8% of refractory cases. Most of the latter were those of partial epilepsy and generalized epilepsy with the monoseizure type. The exacerbation of seizures due to AEDs was also mentioned as one of the important side effects of AEDs.

On the prevalence day, 2,378 epileptic children were identified. Therefore, the prevalence rate for epilepsy was 8.2 per 1,000. The lowest prevalence rate was 1.2 in children under one year of age, and the highest was 11.0 at five years of age. The rate was higher for males than females. The annual incidence rate for epilepsy was estimated at 145.0 per 100,000 for 1975. The onset of seizures was high in the first three years, totaling 1,795 cases (77.7%), and this decreased after four years of age. Primary generalized epilepsy was found in 577 cases (31.7%), secondary generalized epilepsy in 167 (9.2%), partial epilepsy with elementary symptomatology in 205 (11.3%), with complex symptomatology in 61 (3.3%) and partial seizures secondarily generalized in 801 (44.5%). The study on such a number of cases had hitherto never been reported in the world.

A longitudinal clinico-electroencephalographic study was conducted on 484 cases of age-dependent epileptic encephalopathy; early-infantile epileptic encephalopathy with suppression-burst (Ohtahara) (EIEE), the West and Lennox syndromes. 1) The three types had the same kind of etiologic heterogeneity. 2) An evolutional change with age was noted from EIEE to the West and from the West to the Lennox syndromes, with the change from suppression-burst to hypsarhythmia, and from hypsarhythmia to the diffuse slow spike-waves. 3) The core ictal EEG pattern of tonic spasms was the desynchronization in EIEE and the West syndrome, with the rapid synchronization and recruiting rhythm in the Lennox syndrome. In the same cases, the changes from desynchronization to hypersynchronization were observed with age. These facts suggest that the three syndromes are based on the same pathophysiology, strongly related to the subcortical mechanism, and that their clinico-electrical manifestations are modified by the degree of brain maturation.