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Proceedings of the Eighth Conference on Febrile Convulsions, Tokyo, December 14, 1985
strains. Repeated fever-induced seizures did not change the threshold for seizures induced by fever. The water content of the brain decreased. II-I in serum from animals that had had seizures was not elevated compared with that in control serum.
Proceedings of the Eighth Conference on Febrile Convulsions, Tokyo, December 14, 1985
Compiled by Yukio Fukuyama, MD Department of Pediatrics Tokyo Women's Medical College Tokyo
A Study on an Experimental Model of Febrile Convulsions Using the Mouse
Toshiaki Abe, MD, Kiyoko Ogawa, BS, Chizuru Nonaka, MD, Mikio Hiraiwa, MD, Hiroshi Ushijima, MD, Yasuko Fujita, MD, Tomoko Togo, MD and Kazuhiko Ohmi,MD Department of Pediatrics, Teikyo University School ofMedicine, Tokyo A satisfactory model of febrile convulsions (FC) in experimental animals is difficult to design because the definitive etiology of the clinical seizures remains undetermined. The significance of infection and inheritance in the etiology of FC has been described, however, it was incompletely defined. The importance of high fever is generally accepted, so it must be useful for clarification of FC to study experimental animals with convulsions induced by high fever.
Experimental
Three strains of mice CC3H, ICR and DDY) were used throughout the experiment. A mouse was kept for various intervals in a plastic box with a cover, which was immersed in a water bath at various temperatures, 37-50°C. The body temperature was monitored rectally with an electronic thermometer connected to a recorder. After it showed clinical seizures, its body and brain weight were measured. After decapitation, the brain was dissected out and weighed. The water and total lipid contents of the brain were determined. Cholesterol esters in the lipid fraction were determined. The level of Interleukin 1 (11-1) in the serum was estimated.
Results
Febrile seizures were induced when a mouse was kept in the water bath at 50°C for about 10 min. Under these conditions, the body temperature increased almost linearly to 43.1 ± 0.9°C, which was high enough to cause a fever-induced convulsion. The C3H mouse was the most sensitive to high fever among the three
Discussion
Millichap et al described the effects of fever on the threshold for seizures in a few animals. The present results are not consistent with their experimental data for the mouse. We demonstrated differences in the threshold for seizures induced by fever among the three mouse strains. This meant that seizures induced by fever might be determined in part by inherited factors, whether dominant or recessive. Some mice in which a high fever was induced showed retarded growth and looked like dwarf mice. The high fever treatment may have some effect on the hypothalamus-hypophysis system, because the fever center is located in the hypothalamus, where the higher center of growth is also located.
Key words: Febrile convulsion, animal model, mouse strain, threshold, seizures.
Sustained Attention in Children with Febrile Convulsions
Hitoshi Hara, MD, Michiko Hara, MD and Yukio Fukuyama, MD Department of Pediatrics, Tokyo Women's Medical College, Tokyo
A test of sustained attention, a new modified procedure called the continuous performance test (CPT) originally formulated by Rosvold, was carried out for 15 children with febrile convulsions (FC) including 6 cases who were treated with either phenobarbital or carbamazepine, and for 21 normal children.
Materials and Methods
The Tanaka-Binet intelligence test was performed for all subjects for IQ measurement. The children with FC, 9 boys and 6 girls, ranging from 6 years 2 months to 9 years 3 months of age, and the normal children, matched as to sex and age, were divided into three subgroups on the basis of their mental ages (MA); group A with MA of 6 and 7 years, group B with MA of 8 and 9 years, and group C with MA of 10 and 11 years . The three CPT scores, %OE, %CE and EI, were defined as follows.
%OE =
Omission Error x 100 Number of Correct Answers
%CE =
Commission Error 100 Correct Responses + Commission Error x
Error Index (EI) =
V (%OC)2 + (%CE)2
Results
The children with FC showed inferior CPT scores compared to the normal children, or the former scores were greater than the latter. Statistically, or with the Mann-Whitney test, the differences between groups A
Brain & Development, Vol 8, No 5,1986 557
and B were significant; %OE in group B (p < 0.01), %CE in group A (p < 0.05) and group B (p < 0.01), and EI in group A (p < 0.01) and group B (p < 0.01). Conclusion The results of this study suggest that a large percentage of children with FC suffer from a subtle attention deficit irrespective of the frequency of FC attacks, EEG findings or whether an anti-convulsant is given or not. Key words: Sustained attention, continuous perfor· mance test, febrile convulsion.
Analysis of Monoamine Metabolism in Cerebrospinal Fluid in Cases of Febrile Convulsions, BECCT and Absences
Satoshi Kimiya, MD, Tohru Seki, MD, Mariko Maezawa, MD, Tetsuya Yamada, MD, Yasuo Tachibana, MD and Akira Shimizu, MD Department of Pediatrics, School of Medicine, Keio University, Tokyo (SK, TS, MM, TY, YT); Department of Pediatrics, Yamanashi Medical College, Yamanashi (AS)
In investigations on monoamine metabolism in the brain, its metabolites in cerebrospinal fluid are usually measured. Various factors iI)cluding the storage conditions, methods of measurement, patient's ages, concentration gradients, circadian variations, medications and diets should be taken into consideration on assessment of the results. The concentrations of homovanillic acid (HV A) and S-hydroxyindoleacetic acid (S-HIAA) in a control group and in groups of cases of febrile convulsions (FC), untreated absences, and BECCT (Benign Epilepsy of Children with CentroTemporal Foci) were measured. Materials and Methods The control group comprised cases with no evidence of CNS involvement. Cases of aseptic meningitis were included in the control group after they had been cured. The cases of febrile convulsions, absences, and BECCT numbered 12, 6 and 6, respectively. The children in the control, absence, and BECCT groups were kept in bed without food after supper until the lumbar puncture the next morning. The lumbar punctures were performed between 8 AM and 10 AM in the lateral decubitus position. The first 0.5 ml of the CSF was stored at -80°C for analysis, which was performed within a week. HVA and S-HIAA were quantitated with a HPLC apparatus with an electrochemical detector. Results and Discussion The concentrations of HV A and S-HIAA in the CSF were plotted semilogarithmically versus patients' age. In the control group (n = 46), a strong inverse correlation was seen in children between age and log (HV A) or log (S-HIAA) on linear regression analysis (p < 0.001). In the febrile convulsion group (n= 12), the concentrations of S-HIAA were almost the same as those in the control group, whereas for HV A, at the age of 1, distinct concentration variations were detected, from 43.6 ng/ml to 737.9 ng/ml, although
558 Brain & Development, Vol 8, No 5, 1986
no significant variations were detected betw( ages of 2 and 4 compared to the control gro compared the HV A and S-HIAA concentration absence and BECCT groups to those in the group, but no significant difference was detec either group. Dopamine is known as an inhibitory neur mitteL It is usually increased for some time fo convulsions. In the febrile convulsion group, th concentrations varied from 43.6 ng/ml to 737.5 at the age of 1. But the distinct variations COl to the control group could not be explained interval after the cessation of the last com These concentration variations may be related strength or areas of the foci. We could not det the factors which were closely related to th~ concentration in the FC group. We plan to inv( as to whether or not the HV A concentration any correlation to the prognosis of febrile conVL Key words: Monoamine metabolism, cerebr, fluid, epilepsy, febrile convulsion, BECCT, abseJ
Neuron-Specific Enolase (NSE) in Com Diseases of Childhood
Hiroshi Takahashi, MD, Toshihiro Honda, MD, j Tada, MD, Keiichi Takahashi, MD and Chika; tsuka, MD Department of Pediatrics, Juntendo Universit. yasu Hospital, Urayasu, Chiba (HT, CO); Depa. of Pediatrics, Juntendo University School of Me Tokyo (TH, HT, KT)
Enolase is a dimeric enzyme with three subunit i1 and 'Y, which give rise to five isozymes, 0<0<, O<'Y and 'Y'Y. The latter show differential organ di tions. Neurons specifically contain 'Y enolase, has been called neuron-specific enolase (NSEl has been said to be a useful marker for stagil monitoring the response to therapy in patien1 small cell lung cancer and neuroblastomas. In the present study, the NSE levels in seru cerebrospinal fluid (CSF) of cases with epilep febrile convulsions were measured.
0<,
Materials and Methods Serum samples were obtained from 27 patien1 convulsive diseases and 64 control patients, an samples were obtained from 6 patients with con diseases and 47 control patients, respectively. r serum and CSF was measured by means of a , antibody radioimmunoassay. Twenty-tieven serul pies with convulsive diseases included controll~ lepsy (14 cases), uncontrolled epilepsy (11 caSf febrile convulsions (2 cases). Six CSF sample convulsive diseases included uncontrolled epile cases) and febrile convulsions (1 case). Results The mean NSE level in serum from the 64 ( patients was 11.0 ± 3.3 ng/ml and that in CSF the 47 control patients was 7.0 ± 3.0 ng/m!. Th( NSE levels in serum from the 14 cases with con epilepsy and the 11 cases with uncontrolled el were 13.5 ± 4.2 ng/ml and 18.3 ± 6.4 ng/ml, I
tively. The NSE levels in serum of the 2 cases with febrile convulsions were 9.9 and 16.5 ng/ml, respectively. The mean NSE level in CSF from the 5 cases with uncontrolled epilepsy was 5.4 ± 4.0 ng/ml. The NSE level in CSF of the case with febrile convulsions was 2.6 ng/mL There were significant differences in NSE levels between normal controls and controlled epilepsy cases (p < 0.05), normal controls and uncontrolled epilepsy cases (p < 0.001), and controlled epilepsy and uncontrolled epilepsy cases (p < 0.05).
Discussion Tada, one of the present authors, reported that glutamic acid decarboxylase (GAD) activity in CSF of cases with uncontrolled epilepsy or febrile convulsions was higher than that of normal controls or cases of controlled epilepsy . This means that GAD, which is contained exclusively in synapses, might be released into the CSF on injury of the synaptic membrane following a convulsion. NSE activities were higher in the serum of epileptic children than in that of normal controls. This suggests that NSE might be released into the serum (not into the CSF) on injury of the neuronal membrane following a convulsion. Further study is needed to explain the discrepancy between the levels of serum NSE and CSF NSE in epileptic convulsion cases. The serum and CSF NSE levels in the cases with febrile convulsions showed no significant differences from those in normal controls. This means that the neuronal membrane during a febrile convulsion might not be injured , because the cases are few. Key words: Neuron-specific enolase, epilepsy, febrile convulsion.
A Clinical Study on the Effectiveness of Intermittent Therapy with Rectal Diazepam Suppositories for the Prevention of Recurrent Febrile Convulsions: A Further Study
Hiroyuki Shirai, MD, Hisao Miura, MD, Kimio Minagawa, MD and Satoshi Mizuno, MD Department of Pediatrics, Kitasato University School of Medicine, Sagamihara, Kanagawa
The clinical efficacy of intermittent therapy with rectal diazepam (DZP) suppositories for the prevention of recurrent febrile convulsions was studied. The dosage schedule for rectal DZP suppositories was based on the results of pharmacokinetic analysis reported previously.
Subjects and Methods 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 when their temperatures were above 38.0°C. Suppositories containing 0.5 mgJkg of DZP were administered 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 temperature still remained above 38.0°C. No further DZP suppository was administered even if the temperature continued to be elevated. The pa-
tients were followed closely for 6 to 43 months at our pediatric seizure clinic.
Results Of the total 787 febrile episodes of above 38.0°C in all the patients during the follow-up period, DZP suppositories were administered to the patients in 722 cases (91.7%). Thirty-eight of the 133 patients (28.6%) had a total of 58 recurrences of febrile convulsions (7.4% of the total 787 febrile episodes), of which two were observed at 7 and 9 hours after administration of the first DZP suppositor, respectively. In 39 out of the remaining 56 recurrences, the patients were noticed to have fever first after the occurrence of seizures. However, in the other 17 recurrences, DZP suppositories were not administered to the patients arbitrarily, even if 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. Conclusion Intermittent therapy by means of rectal administration of DZP suppositories at home seems to be safe and remarkably effective for the prevention of recurrent febrile convulsions, unless the timing of rectal administration of DZP suppositories is delayed in cases of febrile episodes. Key words: Diazepam, febrile convulsion, rectal administration, suppository.
A Clinical Study on the Effectiveness of Intermittent Therapy with Oral Diazepam Syrups for the Prevention of Recurrent Febrile Convulsions: A Preliminary Report
Midori Hohjo, MD, Hisao Miura, MD, Kimio Minagawa, MD, Takeo Ishidate, MD, Satoshi Mizuno, MD, Hiroyuki Shirai, MD, Wataru Sunaoshi, MD and Yuki Bandoh, MD Department of Pediatrics, Kitasato University School of Medicine, Sagamihara, Kanagawa
Recent studies in Europe have indicated that intermittent therapy with rectal diazepam (DZP) suppositories is effective for preventing recurrent febrile convulsions. However, DZP suppositories are not marketed in Japan. The pesent study was designed to assess clinically whether intermittent administration of oral DZP syrups has a comparable therapeutic efficacy to that of rectal DZP suppositories for the prevention of recurrent febrile convulsions.
Subjects and Methods Forty children aged 8 months to 4 years with two or more previous febrile convulsions were treate? intermittently with oral DZP syrups when their temperatures were above 38.0°C. 0.5 mgfkg of DZP syrups was administered orally to the patients at home as soon as the initial signs of febrile illness were noticed by their parents. A DZP syrup of the same dose was administered again 8 hours after the first dose, when the temperature remained above 38.0°C.
Brain & Development, Vol 8, No 5, 1986 559
No further DZP syrup was administered even if the temperature continued to be elevated. This dosage schedule for oral DZP syrups was based on the results of pharmacokinetic analysis reported previously. The patients were followed closely for 6 to 26 months at our pediatric clinics.
Results
Of the total 112 febrile episodes of above 38.0°C in all the patients during the follow-up period, DZP syrups were administered to the patients in 89 cases (79.5%). Twelve of the 40 patients (30.0%) had a total of 13 recurrences of febrile convulsions (11.6% of the total 112 febrile episodes), none of which was observed after administration of a DZP syrup. In 5 out of the 13 recurrences, the patients were noticed to have fever after the occurrence of seizures. However, in the other 8 recurrences, DZP syrups were not administered to the patients arbitrarily, even if 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.
Conclusion
Intermittent therapy by means of oral administration of DZP syrups at home seems to be safe and remarkably effective for the prevention of recurrent febrile convulsions, unless the timing of oral administration of DZP syrups is delayed in cases of febrile episodes.
Key words: Diazepam, febrile convulsion, intermittent therapy.
Effect of Intermittent Administration of Chloral Hydrate Suppositories for the Prevention of Recurrent Febrile Convulsions (The 2nd Report)
Yasuo Tachibana, MD, Tohru Seki, MD, Hidenori Yamawaki, MD, Nobuyuki Suzuki, MD, Satoshi Kimiya, MD, Mariko Maezawa, MD, Tetsuya Yamada, MD, Akira Shimizu, MD and Tetsuo Yamazaki, MD Department of Pediatrics, Keio University School of Medicine, Tokyo The purpose of this study was to determine whether or not the use of chloral hydrate (CH) suppositories is effective for preventing recurrences of febrile convulsions (FC).
Subjects and Methods
The subjects of this study were 154 children with FC who visited the pediatric department of Keio University Hospital and 6 affiliated hospitals from Feb. 1984 to Jan. 1985, and who were followed for more than six months. They were treated intermittently with CH suppositories or observed without any drugs. For the treated group, we suggested that the parents administer one CH suppository in the case of a body temperature of above 37.5°C, and to administer another after 24 hrs if the fever persisted. The dose of CH was 250 mg for patients weighing less than 15 kg, and 500 mg for patients weighing more than 15 kg.
560 Brain & Development, Vol 8, No 5, 1986
We interviewed the parents, and asked thl all the information concerning the febrile episod recurrences of FC.
Results
1) During the observation period, 127 patieI perienced at least one febrile episode (above 31 Of these, 46 always used CH suppository f febrile illness (Group A), 26 used them only times (Group B) and 55 did not use them at all ( C). The recurrence rates in Groups A, Band i 6.5%, 30.8% and 30.9%, respectively. The din between Groups A and C was statistically signi But the clinical backgrounds of Groups A and, almost the same. 2) Six FC recurred in 136 febrile episodes w suppositories and 40 FC recurred in 151 episodes without CH suppositories. 3) Of the eight cases in Group B with recurreI FC, 2 had FC in each febrile episode irrespec the use of CH suppositories. In the other 6 FC recurred only in febrile episodes when CH sitories were not used. 4) No serious side effects were observed.
Conclusion
Intermittent administration of CH suppositori effective for the prevention of recurrences of F(
Key words: Febrile conVUlsions, treatment, mittent administration, chloral hydrate supposit
The Efficacy of Valproate Sodium Whl EEG Findings Show Deterioration durin phylactic Phenobarbital Therapy for I Convulsions
Kiyoomi Sumi, MD, Yusuke Itagaki, MD, Tagawa, MD and Hyakuji Yabuuchi, MD Pediatric Clinic, Osaka Kohseinenkin Hospital, (KS, YI); Department of Pediatrics, Schoolo. cine, Osaka University, Osaka (TT, HY) Phenobarbital is often used as the prophylactil cation in patients with febrile convulsions (FC findings sometimes show deterioration durir phylactic phenobarbital (PB) therapy. We It the efficacy of valproate sodium (VPA) wh leptic discharges were found to be increased c recording. Six boys and 4 girls were examined. E] discharges were found to be increased in their I cordings after some years of prophylactic PB t: These patients had received VPA, 20-30 mg/I for 3 yrs, instead of PB, then the epileptic dis in 9 cases disappeared and those in 1 case \1 markably reduced. They were divided int groups. The EEG findings in 6 cases improved 11 months (group A), and in the other 4 casl one year (group B) with VPA therapy. The average ages for this examination weI in group A and 11 yrs in group B. The averag tion of clinic attendance was 5 yrs in group 10 yrs in group B. Seven cases could be follO' for more than 5 yrs. There were 5 cases of the simple type (Fuk
1968) and 1 case of the complex type in group A, while the numbers were 3 and 1, respectively, in group B. An incidence of more than 6 seizures was recorded in 1 case (16%) in group A, and in 3 cases (75%) in group B. On the first EEG examination, normal findings were observed in 2 cases, focal spikes of spike & waves in 2, and bilateral spikes or spike & waves in 2 in group A, while focal spikes or spike & waves were observed in 3 cases and bilateral spikes in 1 in group B. The EEG records after some years of PB therapy showed many epileptic discharges in all of the cases. One case showed Rolandic spikes, 4 (4/6) other focal spikes, and 3 bilateral spikes or spike & waves in group A, while 3 cases (3/4) showed Rolandic spikes, 1other focal spikes, 1 generalized spike & waves, and generalized polyspike & waves in group B. Four cases in group A showed normal EEG recordings before 6 months of VPA therapy, while the EEG recordings in 3 cases in group B became normalized after 1-2 yrs. VPA therapy remarkably decreased the epileptic discharges of short duration, when the EEG findings shOWed deterioration during prophylactic PB treatment.
Key words: Febrile convulsion, EEG, valproate sodium, phenobarbital, prophylactic therapy.
Study on Continuous Medication for Cases with Febrile Convulsions over 7 Years Old
Shota Miyake, MD, Sumimasa Yamashita, MD, Michiko Yamada, MD and Hiroko Iwamoto, MD Division of Neurology, Kanagawa Prefectural Children 's Medical Center, Yokohama, Kanagawa
Febrile convulsions (FC) are the most common seizure disorder in childhood, but their actual medicosocial management has not yet been fully agreed upon. The duration of medication is also hotly debated. We studied the clinical and electroencephalographic features of cases who had suffered from FC and who were being treated with continuous medication over the age of 7. Twenty-four boys and 11 girls were examined. The average age at the time of investigation was 9 yrs 10 mos, and the average duration of clinical attendance was 4 yrs 11 mos. PB was used in 28 cases, VPA in 6 and CBZ in 4. It was monopharmacy in all except 3 cases. The average duration of medication was 3 yrs and 11 mos, and the average time from the last attack was 3 yrs and 5 mos. In only 5 cases, 7 attacks occurred despite the continuous medication. Four cases had family histories of epilepsy. Five cases had past histories of probable brain damage in the perinatal period. The onset in 4 cases was before 6 mos or after 5 yrs. Seven cases had prolonged attacks of more than 20 mins, 3 had asymmetric attacks and one of them had accompanying Todd's paresis. Frequent attacks, more than 5 times a year, were observed in 13 cases, and attacks after 7 yrs of age continued in 4 cases. As to Fukuyama's criteria for FC, only 8 cases had simple FC. Serial and detailed
EEG studies showed that all the 35 cases had definite epileptic EEG discharges. So they were categorized as epileptic FC according to Ohtahara's criteria. As to Nelson's criteria, I case had 3 risk factors, 3 had 2 factors and 14 had I factor. The epileptic EEG discharges consisted of diffuse spike & wave bursts (10 cases, 29%), focal spikes (16 cases, 46%), foc al spikes with secondary bilateral synchrony (2 cases, 5%) and focal spikes with mirror foci (7 cases, 20%). But we found pseudopetit-mal discharges in 13 cases, which were omitted from the epileptic discharges. They appeared mostly frequently between the ages of 6 and 9. The loci of these discharges were in the Rolandic area (0, 0-2 yrs; 7, 35 yrs; 12, 6-9 yrs; 3, 10-14 yrs) and in other areas (0, 6, 12 and 8 cases, respectively). The EEG findings were different in the 4 age groups, there being a predominance of normal EEG findings in the youngest group and one of diffuse spike & wave bursts in the second group, while focal spikes were predominant in the two older groups. Once continuous treatment has been started, we feel that there will be much trouble as to the decision when medication must be stopped, especially when the patients have epileptic EEG discharges. The results of this study suggest that epileptic FC over 7 yrs old are closely related to epilepsy. Therefore the medication should be continued until the epileptic EEG discharges disappear.
Key words: Febrile convulsion, epilepsy, continuous anticonvulsant medication, drug termination.
The Clinical Features of Febrile Seizures- An Attempt to Clarify the Seizure Type
Izumi Takahashi, MD, Naoki Yamamoto, MD, Sunao Furune, MD, Kouzaburo Aso, MD, Etsuko Takaesu, MD, Tamiko Negoro, MD, Kazuyoshi Watanabe, MD, Katsuhiro Iwase, MD and Fumio Hayakawa, MD Department of PediatriCS, Nagoya Unviersity Hospital Nagoya, Aichi (IT, NY, SF, KA, ET, TN, KW); Kamo Hospital, Toyota, Aichi (KI); Anjou Kousei Hospital, Anjou, Aichi (FH) There have only been a few descriptions of the clinical features of febrile seizures, probably because they only occur occasionaly and doctors themselves have almost no opportunity to monitor them from the onset. We tried to delineate the ictal fe atures of febrile seizures by means of a detailed interview immediately after a seizure.
Patients and Methods One hundred and sixty-one children were included in this study, who had febrile seizures and were seen at the Nagoya University Hospital or related hospitals from Feb. 1 1985 through Oct. 31 1985. Only mothers who observed at attack well from the beginning were interviewed immediately after the seizure, and as detailed information about the fit as possible was obtained from them. Results and Conclusion The one hundred and seventy-two fits of the 161 children were divided into 3 groups; A) Generalized
Brain & Development, Vol 8, No 5, 1986 561
convulsions starting suddenly without any preceding symptoms, which included tonic, tonic-clonic and clonic seizures. B) Generalized convulsions preceded by some symptoms, such as motionless staring, eye deviation or loss of tone. C) Other fits without movement of the extremities such as motionlessness, staring eyes, eye deviation, focal twitching or automatism. One hundred and one (58.7%) fits belonged to group A, 53 (30.8%) to Band 18 (10.5%) to C, and about one-third of all the febrile seizures were preceded by some symptoms before generalized convulsions. There was no relationship between the ictal features of febrile seizures and age. On the other hand, 88 seizures comprised tonic and/or tonic vibratory convulsions and 46 tonic-clonic convulsions, the former being twice as frequent as the latter. Both groups showed no correlation with age. Among the 161 children, 93 (58%) were diagnosed as having simple febrile seizures and 68 (42%) as having complex febrile seizures, according to the classification of Fukuyama. There was no relationship between the seizure type and the above classification. A followup study is now in progress to determine whether or not there is any relationship between the seizure type and the outcome.
Key words: Febrile seizure, generalized convulsion, clinical ictal feature.
Some Clinical Observations on Febrile Convulsions. Onset after 5 Years of Age
Hideomi Ohta, MD, Atsuhiro Soeda, MD and Kihei Maekawa,MD Department of Pediatrics, Jikei University School of Medicine, Tokyo Febrile convulsions (FC) are usually seen from 6 months to 5 years of age, being rarely seen after 5 years of age. We report some clinical observations in patients who had the first FC after 5 years of age, and who were followed for more than 2 years.
Subjects and Methods In 33 patients with FC (18 male, 15 female), the following factors were inl£flstigated; the age of onset, the seizure type, the duration of the seizure, the postictal stage, the initial electroencephalographic findings and the prognosis after 2 years' follow-up. Results and Conclusion The age of onset: 30 cases had the rust FC between 5 and 7 years of age. But 3 had them at 8, 9 and 12 years of age, respectively. The seizure types: Generalized tonic-clonic seizures were seen in 23 cases, generalized tonic seizures in 6 , generalized clonic seizures in 2, a focal seizure in 1 and an atonic seizure in 1. The duration of the seizure: In 26 cases the seizures were within 5 minutes, in 5 they were between 5 and 10 minutes, and in the other 2 they were more than 20 minutes in duration. The postictal state: 19 cases showed postictal sleep, 5 disturbance of consciousness, 2 headache and 1 nausea. The initial EEG findings: 14 cases showed seizure
562 Brain & Development, Vol 8, No 5,1986
discharges (focal spikes, focal sharp waves, i spike and wave complexes, polyspike and wa plexes, high voltage slow bursts and pseudop discharges), and 8 showed abnormal basic activ The prognosis: Of the 16 cases undergo: phylactic anti-convulsant medication, one had renee of FC and 3 developed epilepsy afterw, the 17 cases undergoing non-prophylactic med 2 had recurrence of FC and one developed e Of the 14 cases who showed abnormal EEG of seizure discharges, 3 developed epilepsy. There was no significant relationship bet\'. prognosis and the prophylactic or non-prop medication, or between the normal EEG and mal EEG groups.
Key words: Febrile conVUlsion, onset after of age, prognosis.
A Clinical Study on Childhood Ep Following Febrile Convulsions (II)
Sumiyoshi Yokoyama, MD, Keiko Tanak, Hideki Konishi, MD, Tadataka Matsui, MD, N, Sadahiro, MD, Soichi Kodama, MD and 1 Matsuo,MD Department of Pediatrics, Kobe University of Medicine, Kobe, Hyogo The authors employed two designs in this stl elucidation of the characteristics of febrile con (FC) in patients who developed epilepsies; comparison of the seizure type, age at on prognosis of childhood epilepsies in patients v had prior FC with those in patients who had prior FC.
Patients and Methods One hundred fifty-six epileptic children and seventy-nine epileptic children were selecte among the outpatients in the Department of Pe of Kobe University Hospital (Group I) and Hin Cross Hospital (Group II), respectively. Of ; epileptic children in Group I, 40 (25 .6%) t prior FC (Epi-FC group), and 116 (74.4%) had prior FC (Epi-non FC group). On the other h (39%) had had prior FC and 48 (61 %) had prior FC in Group II. Results 1) The type of FC in 9 children (22.5%) wa: and 31 (77 .5%) had the complicated type in ( On the othe hand, 16 (51.6%) had the simple Group II . 2) In the Epi-FC group of Group I, the e seizure types consisted of generalized tonic-cl< zures (GTC-57.5%), complex partial seizure 17.5%), secondary generalized epilepsy (SG and others. In the Epi-non FC group of Grou seizure types consisted of SGE (32.8%), GTe CPS (12.1 %) and others. Significant differeJ tween the Epi-FC and Epi-non FC groups wer in GTC and SGE (p < 0.01). In Group II, the no differences in the epileptic seizure patt tween the Epi-FC and Epi-non FC groups. 3) The age at onset of epilepsy was under 4 y
in 11 patients (27.5%) of the Epi-FC group and in 63 (54.3%) of the Epi-non FC group in Group I (p < 0.01), respectively. In Group II, there were no difference in the age at onset of epilepsy. 4) The average number of epileptic attacks in the Epi-non FC group was more than that in the Epi-FC group in Group I, while there was no difference in the number between the Epi-FC and Epi-non FC groups in Group II. Mental retardation was found in 17.5% of the Epi-FC group and in 32.8% of the Epi-non FC group in Group I (p < 0.01), respectively. In Group II, it was found in 19% of the Epi-FC group and in 20% of the Epi-non FC group, respectively.
Key words: Epilepsy, febrile convulsion, anticonvulsant.
A Comparative Study of Febrile Generalized Convulsions with Spikes and Afebrile Generalized Convulsions with Spikes - Clinical Background, EEG Findings and PrognosisSecond Report
Tetsuya Yamada, MD, Tohru Seki, MD, Hidenori Yamawaki, MD, Nobuyuki Suzuki, MD, Satoshi Kimiya, MD, Mariko Maesawa, MD, Yasuo Tachibana, MD and Mitsuhiro Hara, MD Department of Pediatrics, School of Medicine, Keio University, Tokyo
Thirty-one cases of febrile convulsions (FC) (17 boys, 14 girls) and 29 cases of afebrile convulsions (AFC) (11 boys, 18 girls) were studied. Their attacks were generalized in type and one or more paroxysmal discharges were detected in serial EEGs. They were followed over 5 years, and given anticonvulsive drugs. The age at onset ranged from 3 months to 5.7 years old (with a mean of 2.5 years) in the FC group. Therefore only patients age 3 months to 5.7 years (with a mean of 2.7 years) were included in the AFC group.
Results 1) Clinical background: Satistically the two groups had the same background as to sex, perinatal abnormality, family history of epilepsy, frequency of pretreatment attacks of more than 4 times, psycomotor retardation and neurological abnormality. A family history of FC was predominantly high in the FC group. 2) Prognosis: The number of cases which developed into AFC in the FC group was 6 (19.4%). These 6 cases included 2 with one risk factor and 4 with no risk factor. The number of cases with poor prognosis of AFC was 7 (24.1%). Of these 7 cases, 6 had the same risk factor, while remaining one had simple partial seizures. 3) EEG findings (See Table 1): The worst EEG findings were used to categorize the cases, in each age group. The paroxysmal discharges identified in the EEGs of all the patients were examined after division into two groups; an "organic" (including symmetrical synchronous diffuse spike wave complexes and C-PmT of focal paroxysmus) group and a "non-organic" (other than the above) group. Non-organic paroxysmal discharges were found out in a lager number of cases
Table 1
N(FC/AFC)* ** D *** F C-P-mT of F of F 0
0-2
Age group (year) 3-5 6-9
10-14
6/4 0/0 2/2 1/2 1/0
3/9 16/3t 8/13 8/8 0/4
11/4 3/0 11/13 5/8 4/3
7/7 6/5 18/16 16/10 0/1 6t
*: no paroxyamal discharge, * *: diffuse spike wave complexes, ***: focal paroxysmus, t: p < 0.05.
in the AFC group.
Comments Except for that the FC group showed a higher incidence rate for a family history of FC, a common clinical background was found for FC and AFC. There was no significant difference between the ratio of a change from Fe to AFC to a poor prognosis in the AFC group. On the other hand, EEG findings differed between the two groups, i.e. there was a predominance of diffuse spike wave complexes in FC, while occipital paroxysmus was predominant in AFC. And nonorganic paroxysmal discharges were predominant in AFC. From these data, we conclude that some pathophysiological difference must be exist, though almost the same clinical background is found for FC and AFC. Key words: Febrile convulsion, prognosis, EEG
Clinico-Electroencephalographic Study on Febrile Convulsions with Epileptiform EEGs
Hiroshi Fukazawa, MD and Seiji Kimura, MD Pediatric Clinic, Kanagawa Prefectural Ashigarakami Hospital, Matsuda, Kanagawa (HF); Department of Pediatrics, Yokohama City University School of Medicine, Yokohama, Kanagawa (SK) It has been reported that 30 to 40 percent of patients
with febrile convulsions have abnormal EEGs, but these EEGs are not a clear indicator as to the development into epilepsy. The purpose of this paper is to discuss what kinds of epileptiform EEGs show a high risk for development into epilepsy on the basis of a clinico-electroencephalographical comparison between EFC and Epi groups, the definitions of which are given at the head of Materials and Methods.
Materials and Methods One hundred and sixty-nine children with febrile convulsions with epileptiform EEGs, who showed no exact mental or mortor abnormality at the first visit and who had been followed for at least 3 years, were divided into 3 groups; 1) a group with febrile convulsions with epileptiform EEGs who either had no afebrile seizures until 10 years of age or whose epileptiform EEGs had not been seen for the last 2 years (EFC)-103 cases, 2) a group who developed afebrile seizures during the follow-up period as febrile convul-
Brain & Development, Vol 8, No 5, 1986 563
sions with epileptiform EEGs (Epi) - 20 cases, and 3) a group who did not satisfy the above mentioned criteria - 43 cases.
Results Seventeen out of 117 (14.5 %) patients with febrile convulsions with epileptiform EEGs developed epilepsy during anticonvulsant therapy, one patient developed epilepsy after discontinuation of therapy and two out of nine (22.2%) who had been followed without medication developed epilepsy. The types of seizures in the 20 patients with epilepsy were generalized motor seizures (15 cases), absences (2 cases), absence accompanied by generalized motor seizure (1 case) , simple partial motor seizure (1 case) and complex partial seizure (1 case). All of these cases showed a high frequency of epileptiform EEGs on yearly repeated examinations compared to in the EFC group . Focal epileptic discharges are thought to be one of risk factors for developing epilepsy, because none of cases developed epilepsy who had shown only diffuse irregular spike-waves during all their courses. There was no correlation between the focus of the epileptic discharge and the prognosis. A statistically significant difference (p < 0.005), besides that in the EEG findings, between the EFC and Epi groups was found only for mental abnormality, not for other risk factors described previously by Livingstone, Fukuyama and others. Conclusion 1) There was a rather higher incidence in the nonmedica ted group of patients with febrile seizures with epileptiform EEGs developing epilepsy (22.2%) than in the medicated group (14.5%), but the difference was not statistically significant. 2) High frequencies of epileptiform EEGs and focal cortical discharges are thought to be high risk factors for developing epilepsy in patients with febrile seizures with epileptiform EEGs. 3) The presence of mental abnormality is the most dominant risk factor for the development of epilepsy compared to other risk factors, such as EEG abnormality and others. Key words: Febrile convulsions. epileptiform EEGs. epilepsy.
Frequency of Children with Paroxysmal Discharges Seen on EEG in the Normal Population in Hisayama Town
Toru Kurokawa. MD. Makoto Matsuo. MD. Yasufumi Maeda. MD. Kanji Sakamoto. MD and Kohji Ueda. MD Department of Pediatrics. Faculty of Medicine. Kyushu University. Fukuoka
The purpose of this study was to determine the frequency of children with spike-waves and other abnormal paroxysmal discharges, and to clarify their clinical significance in normal children. The materials were 331 5-year-old, 263 6-year-old, 311 7-year-old, 292 8-year-old, 267 9-year-old, 248 10-year-old and 225 ll-year-old children who lived in Hisayama Town, in the vicinity of Fukuoka City. The EEGs were taken with photic stimulation and
564 Brain & Development, Vol 8, No 5, 1986
hyperventilation. The electrodes were applied frontal, central, occipital and temporal regions.
Results 1) Spike discharges were seen in 18 childrer of all the children) in the temporal, in 21 (1 the central, and in 18 (0.9%) in the occipital an other abnormal findings were observed in 14 ( (0.7%). 2) Temporal spikes were seen in 12 children both the awake state and sleep, in 4 during sit in 2 during the awake state; central spikes in 8 both the awake state and sleep, in 5 during sh in 8 during the awake state; occipital spikes iI ing both the awake state and sleep, in 7 durir and in 4 during the awake state; other abnorm ings in 11 during both the awake state and s 2 during sleep and in one during the awake statl 3) Temporal spikes were seen in 10 boys and two had febrile convulsions and 5 epilepsy, and were normal children; central spikes were see: boys and 11 girls; one had febrile convulsio was a sibling of the patient with febrile conv three had epilepsy and seven were normal; 0 spikes were seen in 2 boys and 7 girls; four had convulsions, three were siblings of patients v brile convulsions, one had epilepsy and te: normal; other paroxysmal findings were seen boy and 13 girls; four had febrile convulsions, ( a sibling of a child with febrile convulsions al were normal. Conclusion The frequency of children showing spike dis in the general population in this study was equivalent to that previously reported. Furth! the present study revealed the distributions diseases with spikes and their significance in t. mal population, and the hereditary backgrounc abnormal discharges. Key words: Febrile convulsion, electroencepli phy, epidemiology.
Clinical and Electroencephalographic Stu Siblings with Febrile Convulsions
Takashi Kajitani, MD, Takafumi Kimura, M Mikio Koi, MD Department of Pediatrics. Kawasaki Hospital. saki Medical School. Okayama In order to clarify the genetics of febrile conv (FC), EEG abnormalities associated with FC 2 genetic relationship between FC and childhol lepsy, we conducted a clinical and electroer lographic study on sixty-four siblings. In for siblings both of them had FC and in 20 siblir had FC or grand mal epilepsy developed frc while the others had grand mal epilepsy, pur mal epilepsy or benign epilepsy of childrel ¢entro-temporal EEG foci (BECCT) . These el seizures were easy to control with antiepileptic , With regard to the background activity ir there was similarity in 40 of the 54 siblings (7' whom awake EEG records were obtained . With
to the appearance and localization of the epileptiform discharges, there was concordance in 25 of the 30 siblings (83 %) both of whom showed epileptiform discharges in EEG. In 24 siblings one showed epileptiform discharges and the other did not. In 10 siblings both showed no epileptiform discharges. Most of the epileptiform discharges were diffuse 3-4 cps spikewave bursts, centrotemporal focal spikes (rolandic spikes) or a combination of these discharges. It was suggested that the diffuse 3-4 cps spikewave bursts and rolandic spikes in EEG are inherited, bu t the clinical manifestations corresponding to these epileptiform discharges are not uniform for the same siblings, and that some children with FC are closely related to cases of primary generalized epilepsy (grand mal and pure petit mal epilepsy) occurring in early childhood and BECCT as to the genetic background.
Key words: Febrile convulsions, primary generalized epilepsy, BECCT, diffuse spike-wave burst, rolandic spikes.
EEG Topography in Febrile Convulsions - Significance of Theta Activity
Harumi Yoshinaga, MD and Shunsuke Ohtahara, MD Department of Developmental Neuroscience and Child Neurology, Institute for Neurobiology, Okayama University Medical School, Okayama Many problems remain to be solved concerning the pathophysiology of febrile convulsions (FC). Considering the clues provided by EEG background activity, 103 cases of FC were investigated using the newly developed method for EEG analysis, namely EEG topography. They were classified into three groups: 16 cases of simple Fe, 44 cases of complex FC and 43 cases of epileptic FC.
Methods Electrodes were applied according to the 10/20 international electrode system. In the awake and resting state, the EEG activities during a period of one minute and 10 seconds in 16 areas were analyzed by FFT into six spectral bands; i.e. delta (2 .0-3.5 Hz), theta (4.0-7.5 Hz), alpha, (8.0-9.5 Hz) , alpha. (10.0-12.5 Hz) , beta, (13.0-19.5 Hz) and beta. (20.0-29.5 Hz). A contour map of equivalent potentials, i.e. the square roots of the power intensity, was obtained for each spectral band. Results 1. Dominance of equivalent potentials in each spectral band. According to the dominant area including the maximal equivalent potentials in each spectral band in each age group, the topographic maps were classified into four patterns; frontal dominant, occipital dominant, centro-parietal dominant and unlocalized patterns. The simple FC group showed the same tendencies as the normal group for the delta, theta, alpha, and alpha. bands. On the other hand, differences from the normal group were noted in the theta band in the complex and epileptic Fe groups: the central dominant pattern was predominant. Almost half the cases
showed this pattern even in the age groups over six years when the occipital dominant pattern was observed in 60-70% of normal children. 2. Equivalent potentials in each spectral band Equivalent potentials in the FC group were regarded as abnormal when they deviated by more than ± 2SD from the normative data obtained for 207 normal infants and children, in each spectral band and in each age group. None of the simple Fe group showed abnormality in any spectral bands or areas. On the other hand, a considerable number of cases in the complex and epileptic FC groups showed abnormality in all spectral bands and areas, and most frequently in the theta band. It was noteworthy that a centroparietal abnormality was frequently noted in the complex Fe group. 3. Significance probability mapping (SPM) Both z- and t-maps of SPM were utilized for the objective evaluation of the theta band abnormality in the complex FC group. Many cases with complex FC showed maximal deviation of equivalent potentials from those in the normal group in the left centroparietal area. T-map for the comparison between the groups disclosed the significant deviation of the complex Fe group from the normal group at ages 3-6 years in the left centroparietal area, with a risk under 1%. These findings indicated the significance of the theta activity in the pathophysiology of febrile convulsions and the necessity of further investigation of it.
Key words: Febrile convulsion, EEG topography, significance probability mapping, theta waves.
An Epidemiological Survey of Febrile Convulsions through Regular Health Checks of Infants and Young Children in Suginami-ku Tokyo
Komei Kumagai, MD, Yoko Tolcushige, MD, Keiko Ohkura, MD and Kihei Maekawa, MD Suginami-ku Health Center, Tokyo (YT, KO); Department of Pediatrics, The Jikei University School of Medicine, Tokyo (YT, KM); Department of Pediatrics, Kanagawa Rehabilitation Hospital, Kanagawa Rehabilitation Center, Kanagawa (KK) The aim of this study was to determine the incidence of febrile convulsions through regular health checks at one and a half and 3 years old respectively and basic information for instructing parents as to how to manage the febrile convulsions in their children.
Materials and Methods At routine health checks of 1,199 children aged 18 months and 1,125 children aged three years, between September 1984 and December 1984, the parents were asked about the age at· onset, the type of fit, recurrences, family histories, whether or not EEG had been performed, how they had coped with the fits and how they had obtained knowledge about this condition. Results Twenty-five (2.1%) of the 1,199 younger children had had febrile convulsions by 18 months, and 67 (6%) of the other 1,125 children had had febrile con-
Brain & Development, Vol 8, No 5,1986 565
vulsions by three years. Of the children who had had febrile convulsions in the series as a whole, 4.8% were boys (57 out of 1,178) and 3.1% were girls (35 out of 1,146). Of the latter 92 children, 43% had had their first fit before the age of one year; the descriptions of the fits indicated a tonic-clonic type in 25% and a clonic type in 18%, being unclear in the rest; in 28% there was a family history of febrile convulsions; in 67% no recurrence was reported, 20% had had one recurrence and 13% had had more than one; in 44.6% investigations had included an EEG; measures had been taken to prevent tongue biting in 20.3%, and 13.4% of the children were taken to a doctor immediately. The most common source of knowledge about febrile convulsions for the parents of these children was books, followed by doctors, grandmothers and friends.
Discussion and Conclusion Boys had more frequent episodes of febrile convulsions. Some parents still believe the need to prevent biting of the tongue. The percentage of children who had had EEG examinations had increased compared to that in our former survey in 1984. Key words: Febrile convulsion, epidemiology.
An Epidemiological Study of Febrile Convulsions in Toda City
Sachiko Kanematsu, MD, Fujiko Konjiki, MD, Ekuko Nakada, MD, Makiko Osawa, MD, Masao Iijima, MD and Yukio Fukuyama, MD Department of Pediatrics, Tokyo Women's Medical College, Tokyo (SK, EN, MO, YF); Toda Municipal Health Care Center, Toda, Saitama (FK, MI)
We conducted a population study on febrile convulsions in infancy in Toda City.
Subjects and Methods The subjects were 324 infants, who visited Toda Municipal Health Center from April to November 1985 (inclusive) for regular health checks at 4% years old. They were asked several questions as to convulsions (including their past histories-intrauterine, birth, neonate, etc. - and their family histories of convulsions), and they were physically examined by pediatricians. Results 1) The incidences of febrile convulsions (FC) and afebrile convulsions (AFC), which were calculated on the basis of the data of a health check at 4% years old, were 13.6% and 0.6%, and there was no sexual difference. 2) The clinical features of FC were as follows: The onset of FC - the peak incidence of onset was 20.8 months on average. The number of seizures- 50% of the patients with FC suffered from FC only once. 3) The past histories and family histories of infants with FC and controls were compared. There was no significant difference between the FC group and controls in the incidence of abnormalities during pregnancy or at birth. The incidence of abnormalities in the neonatal period was higher in the FC group
566 Brain & Development, Vol 8, No 5, 1986
(18.6%) than in controls (6.9%). 4) The incidence rate of a family history of 1 predominantly higher in the FC group (34.2~ in controls (5.8%). 5) The status at regular checks: Except for t that the incidence of some abnormal beha tendencies at the 4Y2 years old check was hi; the FC group (45.5%) than in controls (28.8~ incidences of psychomotor delay at 1Y2 and : old checks were nearly the same in the FC gro controls. 6) Infants with FC and some abnormal beha tendencies at 4% years old check showed a incidence of abnormalities in pregnancy, delivt the neonatal period.
Key words: Febrile convulsion, epidemiological health check.
Proceedings of the Eighth Conference on Febrile Convulsions, Tokyo, December 14, 1985
Compiled by Yukio Fukuyama, MD Department of Pediatrics Tokyo Women's Medical College Tokyo
A Study on an Experimental Model of Febrile Convulsions Using the Mouse
Toshiaki Abe, MD, Kiyoko Ogawa, BS, Chizuru Nonaka, MD, Mikio Hiraiwa, MD, Hiroshi Ushijima, MD, Yasuko Fujita, MD, Tomoko Togo, MD and Kazuhiko Ohmi,MD Department of Pediatrics, Teikyo University School ofMedicine, Tokyo A satisfactory model of febrile convulsions (FC) in experimental animals is difficult to design because the definitive etiology of the clinical seizures remains undetermined. The significance of infection and inheritance in the etiology of FC has been described, however, it was incompletely defined. The importance of high fever is generally accepted, so it must be useful for clarification of FC to study experimental animals with convulsions induced by high fever.
Experimental
Three strains of mice CC3H, ICR and DDY) were used throughout the experiment. A mouse was kept for various intervals in a plastic box with a cover, which was immersed in a water bath at various temperatures, 37-50°C. The body temperature was monitored rectally with an electronic thermometer connected to a recorder. After it showed clinical seizures, its body and brain weight were measured. After decapitation, the brain was dissected out and weighed. The water and total lipid contents of the brain were determined. Cholesterol esters in the lipid fraction were determined. The level of Interleukin 1 (11-1) in the serum was estimated.
Results
Febrile seizures were induced when a mouse was kept in the water bath at 50°C for about 10 min. Under these conditions, the body temperature increased almost linearly to 43.1 ± 0.9°C, which was high enough to cause a fever-induced convulsion. The C3H mouse was the most sensitive to high fever among the three
Discussion
Millichap et al described the effects of fever on the threshold for seizures in a few animals. The present results are not consistent with their experimental data for the mouse. We demonstrated differences in the threshold for seizures induced by fever among the three mouse strains. This meant that seizures induced by fever might be determined in part by inherited factors, whether dominant or recessive. Some mice in which a high fever was induced showed retarded growth and looked like dwarf mice. The high fever treatment may have some effect on the hypothalamus-hypophysis system, because the fever center is located in the hypothalamus, where the higher center of growth is also located.
Key words: Febrile convulsion, animal model, mouse strain, threshold, seizures.
Sustained Attention in Children with Febrile Convulsions
Hitoshi Hara, MD, Michiko Hara, MD and Yukio Fukuyama, MD Department of Pediatrics, Tokyo Women's Medical College, Tokyo
A test of sustained attention, a new modified procedure called the continuous performance test (CPT) originally formulated by Rosvold, was carried out for 15 children with febrile convulsions (FC) including 6 cases who were treated with either phenobarbital or carbamazepine, and for 21 normal children.
Materials and Methods
The Tanaka-Binet intelligence test was performed for all subjects for IQ measurement. The children with FC, 9 boys and 6 girls, ranging from 6 years 2 months to 9 years 3 months of age, and the normal children, matched as to sex and age, were divided into three subgroups on the basis of their mental ages (MA); group A with MA of 6 and 7 years, group B with MA of 8 and 9 years, and group C with MA of 10 and 11 years . The three CPT scores, %OE, %CE and EI, were defined as follows.
%OE =
Omission Error x 100 Number of Correct Answers
%CE =
Commission Error 100 Correct Responses + Commission Error x
Error Index (EI) =
V (%OC)2 + (%CE)2
Results
The children with FC showed inferior CPT scores compared to the normal children, or the former scores were greater than the latter. Statistically, or with the Mann-Whitney test, the differences between groups A
Brain & Development, Vol 8, No 5,1986 557
and B were significant; %OE in group B (p < 0.01), %CE in group A (p < 0.05) and group B (p < 0.01), and EI in group A (p < 0.01) and group B (p < 0.01). Conclusion The results of this study suggest that a large percentage of children with FC suffer from a subtle attention deficit irrespective of the frequency of FC attacks, EEG findings or whether an anti-convulsant is given or not. Key words: Sustained attention, continuous perfor· mance test, febrile convulsion.
Analysis of Monoamine Metabolism in Cerebrospinal Fluid in Cases of Febrile Convulsions, BECCT and Absences
Satoshi Kimiya, MD, Tohru Seki, MD, Mariko Maezawa, MD, Tetsuya Yamada, MD, Yasuo Tachibana, MD and Akira Shimizu, MD Department of Pediatrics, School of Medicine, Keio University, Tokyo (SK, TS, MM, TY, YT); Department of Pediatrics, Yamanashi Medical College, Yamanashi (AS)
In investigations on monoamine metabolism in the brain, its metabolites in cerebrospinal fluid are usually measured. Various factors iI)cluding the storage conditions, methods of measurement, patient's ages, concentration gradients, circadian variations, medications and diets should be taken into consideration on assessment of the results. The concentrations of homovanillic acid (HV A) and S-hydroxyindoleacetic acid (S-HIAA) in a control group and in groups of cases of febrile convulsions (FC), untreated absences, and BECCT (Benign Epilepsy of Children with CentroTemporal Foci) were measured. Materials and Methods The control group comprised cases with no evidence of CNS involvement. Cases of aseptic meningitis were included in the control group after they had been cured. The cases of febrile convulsions, absences, and BECCT numbered 12, 6 and 6, respectively. The children in the control, absence, and BECCT groups were kept in bed without food after supper until the lumbar puncture the next morning. The lumbar punctures were performed between 8 AM and 10 AM in the lateral decubitus position. The first 0.5 ml of the CSF was stored at -80°C for analysis, which was performed within a week. HVA and S-HIAA were quantitated with a HPLC apparatus with an electrochemical detector. Results and Discussion The concentrations of HV A and S-HIAA in the CSF were plotted semilogarithmically versus patients' age. In the control group (n = 46), a strong inverse correlation was seen in children between age and log (HV A) or log (S-HIAA) on linear regression analysis (p < 0.001). In the febrile convulsion group (n= 12), the concentrations of S-HIAA were almost the same as those in the control group, whereas for HV A, at the age of 1, distinct concentration variations were detected, from 43.6 ng/ml to 737.9 ng/ml, although
558 Brain & Development, Vol 8, No 5, 1986
no significant variations were detected betw( ages of 2 and 4 compared to the control gro compared the HV A and S-HIAA concentration absence and BECCT groups to those in the group, but no significant difference was detec either group. Dopamine is known as an inhibitory neur mitteL It is usually increased for some time fo convulsions. In the febrile convulsion group, th concentrations varied from 43.6 ng/ml to 737.5 at the age of 1. But the distinct variations COl to the control group could not be explained interval after the cessation of the last com These concentration variations may be related strength or areas of the foci. We could not det the factors which were closely related to th~ concentration in the FC group. We plan to inv( as to whether or not the HV A concentration any correlation to the prognosis of febrile conVL Key words: Monoamine metabolism, cerebr, fluid, epilepsy, febrile convulsion, BECCT, abseJ
Neuron-Specific Enolase (NSE) in Com Diseases of Childhood
Hiroshi Takahashi, MD, Toshihiro Honda, MD, j Tada, MD, Keiichi Takahashi, MD and Chika; tsuka, MD Department of Pediatrics, Juntendo Universit. yasu Hospital, Urayasu, Chiba (HT, CO); Depa. of Pediatrics, Juntendo University School of Me Tokyo (TH, HT, KT)
Enolase is a dimeric enzyme with three subunit i1 and 'Y, which give rise to five isozymes, 0<0<, O<'Y and 'Y'Y. The latter show differential organ di tions. Neurons specifically contain 'Y enolase, has been called neuron-specific enolase (NSEl has been said to be a useful marker for stagil monitoring the response to therapy in patien1 small cell lung cancer and neuroblastomas. In the present study, the NSE levels in seru cerebrospinal fluid (CSF) of cases with epilep febrile convulsions were measured.
0<,
Materials and Methods Serum samples were obtained from 27 patien1 convulsive diseases and 64 control patients, an samples were obtained from 6 patients with con diseases and 47 control patients, respectively. r serum and CSF was measured by means of a , antibody radioimmunoassay. Twenty-tieven serul pies with convulsive diseases included controll~ lepsy (14 cases), uncontrolled epilepsy (11 caSf febrile convulsions (2 cases). Six CSF sample convulsive diseases included uncontrolled epile cases) and febrile convulsions (1 case). Results The mean NSE level in serum from the 64 ( patients was 11.0 ± 3.3 ng/ml and that in CSF the 47 control patients was 7.0 ± 3.0 ng/m!. Th( NSE levels in serum from the 14 cases with con epilepsy and the 11 cases with uncontrolled el were 13.5 ± 4.2 ng/ml and 18.3 ± 6.4 ng/ml, I
tively. The NSE levels in serum of the 2 cases with febrile convulsions were 9.9 and 16.5 ng/ml, respectively. The mean NSE level in CSF from the 5 cases with uncontrolled epilepsy was 5.4 ± 4.0 ng/ml. The NSE level in CSF of the case with febrile convulsions was 2.6 ng/mL There were significant differences in NSE levels between normal controls and controlled epilepsy cases (p < 0.05), normal controls and uncontrolled epilepsy cases (p < 0.001), and controlled epilepsy and uncontrolled epilepsy cases (p < 0.05).
Discussion Tada, one of the present authors, reported that glutamic acid decarboxylase (GAD) activity in CSF of cases with uncontrolled epilepsy or febrile convulsions was higher than that of normal controls or cases of controlled epilepsy . This means that GAD, which is contained exclusively in synapses, might be released into the CSF on injury of the synaptic membrane following a convulsion. NSE activities were higher in the serum of epileptic children than in that of normal controls. This suggests that NSE might be released into the serum (not into the CSF) on injury of the neuronal membrane following a convulsion. Further study is needed to explain the discrepancy between the levels of serum NSE and CSF NSE in epileptic convulsion cases. The serum and CSF NSE levels in the cases with febrile convulsions showed no significant differences from those in normal controls. This means that the neuronal membrane during a febrile convulsion might not be injured , because the cases are few. Key words: Neuron-specific enolase, epilepsy, febrile convulsion.
A Clinical Study on the Effectiveness of Intermittent Therapy with Rectal Diazepam Suppositories for the Prevention of Recurrent Febrile Convulsions: A Further Study
Hiroyuki Shirai, MD, Hisao Miura, MD, Kimio Minagawa, MD and Satoshi Mizuno, MD Department of Pediatrics, Kitasato University School of Medicine, Sagamihara, Kanagawa
The clinical efficacy of intermittent therapy with rectal diazepam (DZP) suppositories for the prevention of recurrent febrile convulsions was studied. The dosage schedule for rectal DZP suppositories was based on the results of pharmacokinetic analysis reported previously.
Subjects and Methods 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 when their temperatures were above 38.0°C. Suppositories containing 0.5 mgJkg of DZP were administered 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 temperature still remained above 38.0°C. No further DZP suppository was administered even if the temperature continued to be elevated. The pa-
tients were followed closely for 6 to 43 months at our pediatric seizure clinic.
Results Of the total 787 febrile episodes of above 38.0°C in all the patients during the follow-up period, DZP suppositories were administered to the patients in 722 cases (91.7%). Thirty-eight of the 133 patients (28.6%) had a total of 58 recurrences of febrile convulsions (7.4% of the total 787 febrile episodes), of which two were observed at 7 and 9 hours after administration of the first DZP suppositor, respectively. In 39 out of the remaining 56 recurrences, the patients were noticed to have fever first after the occurrence of seizures. However, in the other 17 recurrences, DZP suppositories were not administered to the patients arbitrarily, even if 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. Conclusion Intermittent therapy by means of rectal administration of DZP suppositories at home seems to be safe and remarkably effective for the prevention of recurrent febrile convulsions, unless the timing of rectal administration of DZP suppositories is delayed in cases of febrile episodes. Key words: Diazepam, febrile convulsion, rectal administration, suppository.
A Clinical Study on the Effectiveness of Intermittent Therapy with Oral Diazepam Syrups for the Prevention of Recurrent Febrile Convulsions: A Preliminary Report
Midori Hohjo, MD, Hisao Miura, MD, Kimio Minagawa, MD, Takeo Ishidate, MD, Satoshi Mizuno, MD, Hiroyuki Shirai, MD, Wataru Sunaoshi, MD and Yuki Bandoh, MD Department of Pediatrics, Kitasato University School of Medicine, Sagamihara, Kanagawa
Recent studies in Europe have indicated that intermittent therapy with rectal diazepam (DZP) suppositories is effective for preventing recurrent febrile convulsions. However, DZP suppositories are not marketed in Japan. The pesent study was designed to assess clinically whether intermittent administration of oral DZP syrups has a comparable therapeutic efficacy to that of rectal DZP suppositories for the prevention of recurrent febrile convulsions.
Subjects and Methods Forty children aged 8 months to 4 years with two or more previous febrile convulsions were treate? intermittently with oral DZP syrups when their temperatures were above 38.0°C. 0.5 mgfkg of DZP syrups was administered orally to the patients at home as soon as the initial signs of febrile illness were noticed by their parents. A DZP syrup of the same dose was administered again 8 hours after the first dose, when the temperature remained above 38.0°C.
Brain & Development, Vol 8, No 5, 1986 559
No further DZP syrup was administered even if the temperature continued to be elevated. This dosage schedule for oral DZP syrups was based on the results of pharmacokinetic analysis reported previously. The patients were followed closely for 6 to 26 months at our pediatric clinics.
Results
Of the total 112 febrile episodes of above 38.0°C in all the patients during the follow-up period, DZP syrups were administered to the patients in 89 cases (79.5%). Twelve of the 40 patients (30.0%) had a total of 13 recurrences of febrile convulsions (11.6% of the total 112 febrile episodes), none of which was observed after administration of a DZP syrup. In 5 out of the 13 recurrences, the patients were noticed to have fever after the occurrence of seizures. However, in the other 8 recurrences, DZP syrups were not administered to the patients arbitrarily, even if 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.
Conclusion
Intermittent therapy by means of oral administration of DZP syrups at home seems to be safe and remarkably effective for the prevention of recurrent febrile convulsions, unless the timing of oral administration of DZP syrups is delayed in cases of febrile episodes.
Key words: Diazepam, febrile convulsion, intermittent therapy.
Effect of Intermittent Administration of Chloral Hydrate Suppositories for the Prevention of Recurrent Febrile Convulsions (The 2nd Report)
Yasuo Tachibana, MD, Tohru Seki, MD, Hidenori Yamawaki, MD, Nobuyuki Suzuki, MD, Satoshi Kimiya, MD, Mariko Maezawa, MD, Tetsuya Yamada, MD, Akira Shimizu, MD and Tetsuo Yamazaki, MD Department of Pediatrics, Keio University School of Medicine, Tokyo The purpose of this study was to determine whether or not the use of chloral hydrate (CH) suppositories is effective for preventing recurrences of febrile convulsions (FC).
Subjects and Methods
The subjects of this study were 154 children with FC who visited the pediatric department of Keio University Hospital and 6 affiliated hospitals from Feb. 1984 to Jan. 1985, and who were followed for more than six months. They were treated intermittently with CH suppositories or observed without any drugs. For the treated group, we suggested that the parents administer one CH suppository in the case of a body temperature of above 37.5°C, and to administer another after 24 hrs if the fever persisted. The dose of CH was 250 mg for patients weighing less than 15 kg, and 500 mg for patients weighing more than 15 kg.
560 Brain & Development, Vol 8, No 5, 1986
We interviewed the parents, and asked thl all the information concerning the febrile episod recurrences of FC.
Results
1) During the observation period, 127 patieI perienced at least one febrile episode (above 31 Of these, 46 always used CH suppository f febrile illness (Group A), 26 used them only times (Group B) and 55 did not use them at all ( C). The recurrence rates in Groups A, Band i 6.5%, 30.8% and 30.9%, respectively. The din between Groups A and C was statistically signi But the clinical backgrounds of Groups A and, almost the same. 2) Six FC recurred in 136 febrile episodes w suppositories and 40 FC recurred in 151 episodes without CH suppositories. 3) Of the eight cases in Group B with recurreI FC, 2 had FC in each febrile episode irrespec the use of CH suppositories. In the other 6 FC recurred only in febrile episodes when CH sitories were not used. 4) No serious side effects were observed.
Conclusion
Intermittent administration of CH suppositori effective for the prevention of recurrences of F(
Key words: Febrile conVUlsions, treatment, mittent administration, chloral hydrate supposit
The Efficacy of Valproate Sodium Whl EEG Findings Show Deterioration durin phylactic Phenobarbital Therapy for I Convulsions
Kiyoomi Sumi, MD, Yusuke Itagaki, MD, Tagawa, MD and Hyakuji Yabuuchi, MD Pediatric Clinic, Osaka Kohseinenkin Hospital, (KS, YI); Department of Pediatrics, Schoolo. cine, Osaka University, Osaka (TT, HY) Phenobarbital is often used as the prophylactil cation in patients with febrile convulsions (FC findings sometimes show deterioration durir phylactic phenobarbital (PB) therapy. We It the efficacy of valproate sodium (VPA) wh leptic discharges were found to be increased c recording. Six boys and 4 girls were examined. E] discharges were found to be increased in their I cordings after some years of prophylactic PB t: These patients had received VPA, 20-30 mg/I for 3 yrs, instead of PB, then the epileptic dis in 9 cases disappeared and those in 1 case \1 markably reduced. They were divided int groups. The EEG findings in 6 cases improved 11 months (group A), and in the other 4 casl one year (group B) with VPA therapy. The average ages for this examination weI in group A and 11 yrs in group B. The averag tion of clinic attendance was 5 yrs in group 10 yrs in group B. Seven cases could be follO' for more than 5 yrs. There were 5 cases of the simple type (Fuk
1968) and 1 case of the complex type in group A, while the numbers were 3 and 1, respectively, in group B. An incidence of more than 6 seizures was recorded in 1 case (16%) in group A, and in 3 cases (75%) in group B. On the first EEG examination, normal findings were observed in 2 cases, focal spikes of spike & waves in 2, and bilateral spikes or spike & waves in 2 in group A, while focal spikes or spike & waves were observed in 3 cases and bilateral spikes in 1 in group B. The EEG records after some years of PB therapy showed many epileptic discharges in all of the cases. One case showed Rolandic spikes, 4 (4/6) other focal spikes, and 3 bilateral spikes or spike & waves in group A, while 3 cases (3/4) showed Rolandic spikes, 1other focal spikes, 1 generalized spike & waves, and generalized polyspike & waves in group B. Four cases in group A showed normal EEG recordings before 6 months of VPA therapy, while the EEG recordings in 3 cases in group B became normalized after 1-2 yrs. VPA therapy remarkably decreased the epileptic discharges of short duration, when the EEG findings shOWed deterioration during prophylactic PB treatment.
Key words: Febrile convulsion, EEG, valproate sodium, phenobarbital, prophylactic therapy.
Study on Continuous Medication for Cases with Febrile Convulsions over 7 Years Old
Shota Miyake, MD, Sumimasa Yamashita, MD, Michiko Yamada, MD and Hiroko Iwamoto, MD Division of Neurology, Kanagawa Prefectural Children 's Medical Center, Yokohama, Kanagawa
Febrile convulsions (FC) are the most common seizure disorder in childhood, but their actual medicosocial management has not yet been fully agreed upon. The duration of medication is also hotly debated. We studied the clinical and electroencephalographic features of cases who had suffered from FC and who were being treated with continuous medication over the age of 7. Twenty-four boys and 11 girls were examined. The average age at the time of investigation was 9 yrs 10 mos, and the average duration of clinical attendance was 4 yrs 11 mos. PB was used in 28 cases, VPA in 6 and CBZ in 4. It was monopharmacy in all except 3 cases. The average duration of medication was 3 yrs and 11 mos, and the average time from the last attack was 3 yrs and 5 mos. In only 5 cases, 7 attacks occurred despite the continuous medication. Four cases had family histories of epilepsy. Five cases had past histories of probable brain damage in the perinatal period. The onset in 4 cases was before 6 mos or after 5 yrs. Seven cases had prolonged attacks of more than 20 mins, 3 had asymmetric attacks and one of them had accompanying Todd's paresis. Frequent attacks, more than 5 times a year, were observed in 13 cases, and attacks after 7 yrs of age continued in 4 cases. As to Fukuyama's criteria for FC, only 8 cases had simple FC. Serial and detailed
EEG studies showed that all the 35 cases had definite epileptic EEG discharges. So they were categorized as epileptic FC according to Ohtahara's criteria. As to Nelson's criteria, I case had 3 risk factors, 3 had 2 factors and 14 had I factor. The epileptic EEG discharges consisted of diffuse spike & wave bursts (10 cases, 29%), focal spikes (16 cases, 46%), foc al spikes with secondary bilateral synchrony (2 cases, 5%) and focal spikes with mirror foci (7 cases, 20%). But we found pseudopetit-mal discharges in 13 cases, which were omitted from the epileptic discharges. They appeared mostly frequently between the ages of 6 and 9. The loci of these discharges were in the Rolandic area (0, 0-2 yrs; 7, 35 yrs; 12, 6-9 yrs; 3, 10-14 yrs) and in other areas (0, 6, 12 and 8 cases, respectively). The EEG findings were different in the 4 age groups, there being a predominance of normal EEG findings in the youngest group and one of diffuse spike & wave bursts in the second group, while focal spikes were predominant in the two older groups. Once continuous treatment has been started, we feel that there will be much trouble as to the decision when medication must be stopped, especially when the patients have epileptic EEG discharges. The results of this study suggest that epileptic FC over 7 yrs old are closely related to epilepsy. Therefore the medication should be continued until the epileptic EEG discharges disappear.
Key words: Febrile convulsion, epilepsy, continuous anticonvulsant medication, drug termination.
The Clinical Features of Febrile Seizures- An Attempt to Clarify the Seizure Type
Izumi Takahashi, MD, Naoki Yamamoto, MD, Sunao Furune, MD, Kouzaburo Aso, MD, Etsuko Takaesu, MD, Tamiko Negoro, MD, Kazuyoshi Watanabe, MD, Katsuhiro Iwase, MD and Fumio Hayakawa, MD Department of PediatriCS, Nagoya Unviersity Hospital Nagoya, Aichi (IT, NY, SF, KA, ET, TN, KW); Kamo Hospital, Toyota, Aichi (KI); Anjou Kousei Hospital, Anjou, Aichi (FH) There have only been a few descriptions of the clinical features of febrile seizures, probably because they only occur occasionaly and doctors themselves have almost no opportunity to monitor them from the onset. We tried to delineate the ictal fe atures of febrile seizures by means of a detailed interview immediately after a seizure.
Patients and Methods One hundred and sixty-one children were included in this study, who had febrile seizures and were seen at the Nagoya University Hospital or related hospitals from Feb. 1 1985 through Oct. 31 1985. Only mothers who observed at attack well from the beginning were interviewed immediately after the seizure, and as detailed information about the fit as possible was obtained from them. Results and Conclusion The one hundred and seventy-two fits of the 161 children were divided into 3 groups; A) Generalized
Brain & Development, Vol 8, No 5, 1986 561
convulsions starting suddenly without any preceding symptoms, which included tonic, tonic-clonic and clonic seizures. B) Generalized convulsions preceded by some symptoms, such as motionless staring, eye deviation or loss of tone. C) Other fits without movement of the extremities such as motionlessness, staring eyes, eye deviation, focal twitching or automatism. One hundred and one (58.7%) fits belonged to group A, 53 (30.8%) to Band 18 (10.5%) to C, and about one-third of all the febrile seizures were preceded by some symptoms before generalized convulsions. There was no relationship between the ictal features of febrile seizures and age. On the other hand, 88 seizures comprised tonic and/or tonic vibratory convulsions and 46 tonic-clonic convulsions, the former being twice as frequent as the latter. Both groups showed no correlation with age. Among the 161 children, 93 (58%) were diagnosed as having simple febrile seizures and 68 (42%) as having complex febrile seizures, according to the classification of Fukuyama. There was no relationship between the seizure type and the above classification. A followup study is now in progress to determine whether or not there is any relationship between the seizure type and the outcome.
Key words: Febrile seizure, generalized convulsion, clinical ictal feature.
Some Clinical Observations on Febrile Convulsions. Onset after 5 Years of Age
Hideomi Ohta, MD, Atsuhiro Soeda, MD and Kihei Maekawa,MD Department of Pediatrics, Jikei University School of Medicine, Tokyo Febrile convulsions (FC) are usually seen from 6 months to 5 years of age, being rarely seen after 5 years of age. We report some clinical observations in patients who had the first FC after 5 years of age, and who were followed for more than 2 years.
Subjects and Methods In 33 patients with FC (18 male, 15 female), the following factors were inl£flstigated; the age of onset, the seizure type, the duration of the seizure, the postictal stage, the initial electroencephalographic findings and the prognosis after 2 years' follow-up. Results and Conclusion The age of onset: 30 cases had the rust FC between 5 and 7 years of age. But 3 had them at 8, 9 and 12 years of age, respectively. The seizure types: Generalized tonic-clonic seizures were seen in 23 cases, generalized tonic seizures in 6 , generalized clonic seizures in 2, a focal seizure in 1 and an atonic seizure in 1. The duration of the seizure: In 26 cases the seizures were within 5 minutes, in 5 they were between 5 and 10 minutes, and in the other 2 they were more than 20 minutes in duration. The postictal state: 19 cases showed postictal sleep, 5 disturbance of consciousness, 2 headache and 1 nausea. The initial EEG findings: 14 cases showed seizure
562 Brain & Development, Vol 8, No 5,1986
discharges (focal spikes, focal sharp waves, i spike and wave complexes, polyspike and wa plexes, high voltage slow bursts and pseudop discharges), and 8 showed abnormal basic activ The prognosis: Of the 16 cases undergo: phylactic anti-convulsant medication, one had renee of FC and 3 developed epilepsy afterw, the 17 cases undergoing non-prophylactic med 2 had recurrence of FC and one developed e Of the 14 cases who showed abnormal EEG of seizure discharges, 3 developed epilepsy. There was no significant relationship bet\'. prognosis and the prophylactic or non-prop medication, or between the normal EEG and mal EEG groups.
Key words: Febrile conVUlsion, onset after of age, prognosis.
A Clinical Study on Childhood Ep Following Febrile Convulsions (II)
Sumiyoshi Yokoyama, MD, Keiko Tanak, Hideki Konishi, MD, Tadataka Matsui, MD, N, Sadahiro, MD, Soichi Kodama, MD and 1 Matsuo,MD Department of Pediatrics, Kobe University of Medicine, Kobe, Hyogo The authors employed two designs in this stl elucidation of the characteristics of febrile con (FC) in patients who developed epilepsies; comparison of the seizure type, age at on prognosis of childhood epilepsies in patients v had prior FC with those in patients who had prior FC.
Patients and Methods One hundred fifty-six epileptic children and seventy-nine epileptic children were selecte among the outpatients in the Department of Pe of Kobe University Hospital (Group I) and Hin Cross Hospital (Group II), respectively. Of ; epileptic children in Group I, 40 (25 .6%) t prior FC (Epi-FC group), and 116 (74.4%) had prior FC (Epi-non FC group). On the other h (39%) had had prior FC and 48 (61 %) had prior FC in Group II. Results 1) The type of FC in 9 children (22.5%) wa: and 31 (77 .5%) had the complicated type in ( On the othe hand, 16 (51.6%) had the simple Group II . 2) In the Epi-FC group of Group I, the e seizure types consisted of generalized tonic-cl< zures (GTC-57.5%), complex partial seizure 17.5%), secondary generalized epilepsy (SG and others. In the Epi-non FC group of Grou seizure types consisted of SGE (32.8%), GTe CPS (12.1 %) and others. Significant differeJ tween the Epi-FC and Epi-non FC groups wer in GTC and SGE (p < 0.01). In Group II, the no differences in the epileptic seizure patt tween the Epi-FC and Epi-non FC groups. 3) The age at onset of epilepsy was under 4 y
in 11 patients (27.5%) of the Epi-FC group and in 63 (54.3%) of the Epi-non FC group in Group I (p < 0.01), respectively. In Group II, there were no difference in the age at onset of epilepsy. 4) The average number of epileptic attacks in the Epi-non FC group was more than that in the Epi-FC group in Group I, while there was no difference in the number between the Epi-FC and Epi-non FC groups in Group II. Mental retardation was found in 17.5% of the Epi-FC group and in 32.8% of the Epi-non FC group in Group I (p < 0.01), respectively. In Group II, it was found in 19% of the Epi-FC group and in 20% of the Epi-non FC group, respectively.
Key words: Epilepsy, febrile convulsion, anticonvulsant.
A Comparative Study of Febrile Generalized Convulsions with Spikes and Afebrile Generalized Convulsions with Spikes - Clinical Background, EEG Findings and PrognosisSecond Report
Tetsuya Yamada, MD, Tohru Seki, MD, Hidenori Yamawaki, MD, Nobuyuki Suzuki, MD, Satoshi Kimiya, MD, Mariko Maesawa, MD, Yasuo Tachibana, MD and Mitsuhiro Hara, MD Department of Pediatrics, School of Medicine, Keio University, Tokyo
Thirty-one cases of febrile convulsions (FC) (17 boys, 14 girls) and 29 cases of afebrile convulsions (AFC) (11 boys, 18 girls) were studied. Their attacks were generalized in type and one or more paroxysmal discharges were detected in serial EEGs. They were followed over 5 years, and given anticonvulsive drugs. The age at onset ranged from 3 months to 5.7 years old (with a mean of 2.5 years) in the FC group. Therefore only patients age 3 months to 5.7 years (with a mean of 2.7 years) were included in the AFC group.
Results 1) Clinical background: Satistically the two groups had the same background as to sex, perinatal abnormality, family history of epilepsy, frequency of pretreatment attacks of more than 4 times, psycomotor retardation and neurological abnormality. A family history of FC was predominantly high in the FC group. 2) Prognosis: The number of cases which developed into AFC in the FC group was 6 (19.4%). These 6 cases included 2 with one risk factor and 4 with no risk factor. The number of cases with poor prognosis of AFC was 7 (24.1%). Of these 7 cases, 6 had the same risk factor, while remaining one had simple partial seizures. 3) EEG findings (See Table 1): The worst EEG findings were used to categorize the cases, in each age group. The paroxysmal discharges identified in the EEGs of all the patients were examined after division into two groups; an "organic" (including symmetrical synchronous diffuse spike wave complexes and C-PmT of focal paroxysmus) group and a "non-organic" (other than the above) group. Non-organic paroxysmal discharges were found out in a lager number of cases
Table 1
N(FC/AFC)* ** D *** F C-P-mT of F of F 0
0-2
Age group (year) 3-5 6-9
10-14
6/4 0/0 2/2 1/2 1/0
3/9 16/3t 8/13 8/8 0/4
11/4 3/0 11/13 5/8 4/3
7/7 6/5 18/16 16/10 0/1 6t
*: no paroxyamal discharge, * *: diffuse spike wave complexes, ***: focal paroxysmus, t: p < 0.05.
in the AFC group.
Comments Except for that the FC group showed a higher incidence rate for a family history of FC, a common clinical background was found for FC and AFC. There was no significant difference between the ratio of a change from Fe to AFC to a poor prognosis in the AFC group. On the other hand, EEG findings differed between the two groups, i.e. there was a predominance of diffuse spike wave complexes in FC, while occipital paroxysmus was predominant in AFC. And nonorganic paroxysmal discharges were predominant in AFC. From these data, we conclude that some pathophysiological difference must be exist, though almost the same clinical background is found for FC and AFC. Key words: Febrile convulsion, prognosis, EEG
Clinico-Electroencephalographic Study on Febrile Convulsions with Epileptiform EEGs
Hiroshi Fukazawa, MD and Seiji Kimura, MD Pediatric Clinic, Kanagawa Prefectural Ashigarakami Hospital, Matsuda, Kanagawa (HF); Department of Pediatrics, Yokohama City University School of Medicine, Yokohama, Kanagawa (SK) It has been reported that 30 to 40 percent of patients
with febrile convulsions have abnormal EEGs, but these EEGs are not a clear indicator as to the development into epilepsy. The purpose of this paper is to discuss what kinds of epileptiform EEGs show a high risk for development into epilepsy on the basis of a clinico-electroencephalographical comparison between EFC and Epi groups, the definitions of which are given at the head of Materials and Methods.
Materials and Methods One hundred and sixty-nine children with febrile convulsions with epileptiform EEGs, who showed no exact mental or mortor abnormality at the first visit and who had been followed for at least 3 years, were divided into 3 groups; 1) a group with febrile convulsions with epileptiform EEGs who either had no afebrile seizures until 10 years of age or whose epileptiform EEGs had not been seen for the last 2 years (EFC)-103 cases, 2) a group who developed afebrile seizures during the follow-up period as febrile convul-
Brain & Development, Vol 8, No 5, 1986 563
sions with epileptiform EEGs (Epi) - 20 cases, and 3) a group who did not satisfy the above mentioned criteria - 43 cases.
Results Seventeen out of 117 (14.5 %) patients with febrile convulsions with epileptiform EEGs developed epilepsy during anticonvulsant therapy, one patient developed epilepsy after discontinuation of therapy and two out of nine (22.2%) who had been followed without medication developed epilepsy. The types of seizures in the 20 patients with epilepsy were generalized motor seizures (15 cases), absences (2 cases), absence accompanied by generalized motor seizure (1 case) , simple partial motor seizure (1 case) and complex partial seizure (1 case). All of these cases showed a high frequency of epileptiform EEGs on yearly repeated examinations compared to in the EFC group . Focal epileptic discharges are thought to be one of risk factors for developing epilepsy, because none of cases developed epilepsy who had shown only diffuse irregular spike-waves during all their courses. There was no correlation between the focus of the epileptic discharge and the prognosis. A statistically significant difference (p < 0.005), besides that in the EEG findings, between the EFC and Epi groups was found only for mental abnormality, not for other risk factors described previously by Livingstone, Fukuyama and others. Conclusion 1) There was a rather higher incidence in the nonmedica ted group of patients with febrile seizures with epileptiform EEGs developing epilepsy (22.2%) than in the medicated group (14.5%), but the difference was not statistically significant. 2) High frequencies of epileptiform EEGs and focal cortical discharges are thought to be high risk factors for developing epilepsy in patients with febrile seizures with epileptiform EEGs. 3) The presence of mental abnormality is the most dominant risk factor for the development of epilepsy compared to other risk factors, such as EEG abnormality and others. Key words: Febrile convulsions. epileptiform EEGs. epilepsy.
Frequency of Children with Paroxysmal Discharges Seen on EEG in the Normal Population in Hisayama Town
Toru Kurokawa. MD. Makoto Matsuo. MD. Yasufumi Maeda. MD. Kanji Sakamoto. MD and Kohji Ueda. MD Department of Pediatrics. Faculty of Medicine. Kyushu University. Fukuoka
The purpose of this study was to determine the frequency of children with spike-waves and other abnormal paroxysmal discharges, and to clarify their clinical significance in normal children. The materials were 331 5-year-old, 263 6-year-old, 311 7-year-old, 292 8-year-old, 267 9-year-old, 248 10-year-old and 225 ll-year-old children who lived in Hisayama Town, in the vicinity of Fukuoka City. The EEGs were taken with photic stimulation and
564 Brain & Development, Vol 8, No 5, 1986
hyperventilation. The electrodes were applied frontal, central, occipital and temporal regions.
Results 1) Spike discharges were seen in 18 childrer of all the children) in the temporal, in 21 (1 the central, and in 18 (0.9%) in the occipital an other abnormal findings were observed in 14 ( (0.7%). 2) Temporal spikes were seen in 12 children both the awake state and sleep, in 4 during sit in 2 during the awake state; central spikes in 8 both the awake state and sleep, in 5 during sh in 8 during the awake state; occipital spikes iI ing both the awake state and sleep, in 7 durir and in 4 during the awake state; other abnorm ings in 11 during both the awake state and s 2 during sleep and in one during the awake statl 3) Temporal spikes were seen in 10 boys and two had febrile convulsions and 5 epilepsy, and were normal children; central spikes were see: boys and 11 girls; one had febrile convulsio was a sibling of the patient with febrile conv three had epilepsy and seven were normal; 0 spikes were seen in 2 boys and 7 girls; four had convulsions, three were siblings of patients v brile convulsions, one had epilepsy and te: normal; other paroxysmal findings were seen boy and 13 girls; four had febrile convulsions, ( a sibling of a child with febrile convulsions al were normal. Conclusion The frequency of children showing spike dis in the general population in this study was equivalent to that previously reported. Furth! the present study revealed the distributions diseases with spikes and their significance in t. mal population, and the hereditary backgrounc abnormal discharges. Key words: Febrile convulsion, electroencepli phy, epidemiology.
Clinical and Electroencephalographic Stu Siblings with Febrile Convulsions
Takashi Kajitani, MD, Takafumi Kimura, M Mikio Koi, MD Department of Pediatrics. Kawasaki Hospital. saki Medical School. Okayama In order to clarify the genetics of febrile conv (FC), EEG abnormalities associated with FC 2 genetic relationship between FC and childhol lepsy, we conducted a clinical and electroer lographic study on sixty-four siblings. In for siblings both of them had FC and in 20 siblir had FC or grand mal epilepsy developed frc while the others had grand mal epilepsy, pur mal epilepsy or benign epilepsy of childrel ¢entro-temporal EEG foci (BECCT) . These el seizures were easy to control with antiepileptic , With regard to the background activity ir there was similarity in 40 of the 54 siblings (7' whom awake EEG records were obtained . With
to the appearance and localization of the epileptiform discharges, there was concordance in 25 of the 30 siblings (83 %) both of whom showed epileptiform discharges in EEG. In 24 siblings one showed epileptiform discharges and the other did not. In 10 siblings both showed no epileptiform discharges. Most of the epileptiform discharges were diffuse 3-4 cps spikewave bursts, centrotemporal focal spikes (rolandic spikes) or a combination of these discharges. It was suggested that the diffuse 3-4 cps spikewave bursts and rolandic spikes in EEG are inherited, bu t the clinical manifestations corresponding to these epileptiform discharges are not uniform for the same siblings, and that some children with FC are closely related to cases of primary generalized epilepsy (grand mal and pure petit mal epilepsy) occurring in early childhood and BECCT as to the genetic background.
Key words: Febrile convulsions, primary generalized epilepsy, BECCT, diffuse spike-wave burst, rolandic spikes.
EEG Topography in Febrile Convulsions - Significance of Theta Activity
Harumi Yoshinaga, MD and Shunsuke Ohtahara, MD Department of Developmental Neuroscience and Child Neurology, Institute for Neurobiology, Okayama University Medical School, Okayama Many problems remain to be solved concerning the pathophysiology of febrile convulsions (FC). Considering the clues provided by EEG background activity, 103 cases of FC were investigated using the newly developed method for EEG analysis, namely EEG topography. They were classified into three groups: 16 cases of simple Fe, 44 cases of complex FC and 43 cases of epileptic FC.
Methods Electrodes were applied according to the 10/20 international electrode system. In the awake and resting state, the EEG activities during a period of one minute and 10 seconds in 16 areas were analyzed by FFT into six spectral bands; i.e. delta (2 .0-3.5 Hz), theta (4.0-7.5 Hz), alpha, (8.0-9.5 Hz) , alpha. (10.0-12.5 Hz) , beta, (13.0-19.5 Hz) and beta. (20.0-29.5 Hz). A contour map of equivalent potentials, i.e. the square roots of the power intensity, was obtained for each spectral band. Results 1. Dominance of equivalent potentials in each spectral band. According to the dominant area including the maximal equivalent potentials in each spectral band in each age group, the topographic maps were classified into four patterns; frontal dominant, occipital dominant, centro-parietal dominant and unlocalized patterns. The simple FC group showed the same tendencies as the normal group for the delta, theta, alpha, and alpha. bands. On the other hand, differences from the normal group were noted in the theta band in the complex and epileptic Fe groups: the central dominant pattern was predominant. Almost half the cases
showed this pattern even in the age groups over six years when the occipital dominant pattern was observed in 60-70% of normal children. 2. Equivalent potentials in each spectral band Equivalent potentials in the FC group were regarded as abnormal when they deviated by more than ± 2SD from the normative data obtained for 207 normal infants and children, in each spectral band and in each age group. None of the simple Fe group showed abnormality in any spectral bands or areas. On the other hand, a considerable number of cases in the complex and epileptic FC groups showed abnormality in all spectral bands and areas, and most frequently in the theta band. It was noteworthy that a centroparietal abnormality was frequently noted in the complex Fe group. 3. Significance probability mapping (SPM) Both z- and t-maps of SPM were utilized for the objective evaluation of the theta band abnormality in the complex FC group. Many cases with complex FC showed maximal deviation of equivalent potentials from those in the normal group in the left centroparietal area. T-map for the comparison between the groups disclosed the significant deviation of the complex Fe group from the normal group at ages 3-6 years in the left centroparietal area, with a risk under 1%. These findings indicated the significance of the theta activity in the pathophysiology of febrile convulsions and the necessity of further investigation of it.
Key words: Febrile convulsion, EEG topography, significance probability mapping, theta waves.
An Epidemiological Survey of Febrile Convulsions through Regular Health Checks of Infants and Young Children in Suginami-ku Tokyo
Komei Kumagai, MD, Yoko Tolcushige, MD, Keiko Ohkura, MD and Kihei Maekawa, MD Suginami-ku Health Center, Tokyo (YT, KO); Department of Pediatrics, The Jikei University School of Medicine, Tokyo (YT, KM); Department of Pediatrics, Kanagawa Rehabilitation Hospital, Kanagawa Rehabilitation Center, Kanagawa (KK) The aim of this study was to determine the incidence of febrile convulsions through regular health checks at one and a half and 3 years old respectively and basic information for instructing parents as to how to manage the febrile convulsions in their children.
Materials and Methods At routine health checks of 1,199 children aged 18 months and 1,125 children aged three years, between September 1984 and December 1984, the parents were asked about the age at· onset, the type of fit, recurrences, family histories, whether or not EEG had been performed, how they had coped with the fits and how they had obtained knowledge about this condition. Results Twenty-five (2.1%) of the 1,199 younger children had had febrile convulsions by 18 months, and 67 (6%) of the other 1,125 children had had febrile con-
Brain & Development, Vol 8, No 5,1986 565
vulsions by three years. Of the children who had had febrile convulsions in the series as a whole, 4.8% were boys (57 out of 1,178) and 3.1% were girls (35 out of 1,146). Of the latter 92 children, 43% had had their first fit before the age of one year; the descriptions of the fits indicated a tonic-clonic type in 25% and a clonic type in 18%, being unclear in the rest; in 28% there was a family history of febrile convulsions; in 67% no recurrence was reported, 20% had had one recurrence and 13% had had more than one; in 44.6% investigations had included an EEG; measures had been taken to prevent tongue biting in 20.3%, and 13.4% of the children were taken to a doctor immediately. The most common source of knowledge about febrile convulsions for the parents of these children was books, followed by doctors, grandmothers and friends.
Discussion and Conclusion Boys had more frequent episodes of febrile convulsions. Some parents still believe the need to prevent biting of the tongue. The percentage of children who had had EEG examinations had increased compared to that in our former survey in 1984. Key words: Febrile convulsion, epidemiology.
An Epidemiological Study of Febrile Convulsions in Toda City
Sachiko Kanematsu, MD, Fujiko Konjiki, MD, Ekuko Nakada, MD, Makiko Osawa, MD, Masao Iijima, MD and Yukio Fukuyama, MD Department of Pediatrics, Tokyo Women's Medical College, Tokyo (SK, EN, MO, YF); Toda Municipal Health Care Center, Toda, Saitama (FK, MI)
We conducted a population study on febrile convulsions in infancy in Toda City.
Subjects and Methods The subjects were 324 infants, who visited Toda Municipal Health Center from April to November 1985 (inclusive) for regular health checks at 4% years old. They were asked several questions as to convulsions (including their past histories-intrauterine, birth, neonate, etc. - and their family histories of convulsions), and they were physically examined by pediatricians. Results 1) The incidences of febrile convulsions (FC) and afebrile convulsions (AFC), which were calculated on the basis of the data of a health check at 4% years old, were 13.6% and 0.6%, and there was no sexual difference. 2) The clinical features of FC were as follows: The onset of FC - the peak incidence of onset was 20.8 months on average. The number of seizures- 50% of the patients with FC suffered from FC only once. 3) The past histories and family histories of infants with FC and controls were compared. There was no significant difference between the FC group and controls in the incidence of abnormalities during pregnancy or at birth. The incidence of abnormalities in the neonatal period was higher in the FC group
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(18.6%) than in controls (6.9%). 4) The incidence rate of a family history of 1 predominantly higher in the FC group (34.2~ in controls (5.8%). 5) The status at regular checks: Except for t that the incidence of some abnormal beha tendencies at the 4Y2 years old check was hi; the FC group (45.5%) than in controls (28.8~ incidences of psychomotor delay at 1Y2 and : old checks were nearly the same in the FC gro controls. 6) Infants with FC and some abnormal beha tendencies at 4% years old check showed a incidence of abnormalities in pregnancy, delivt the neonatal period.
Key words: Febrile convulsion, epidemiological health check.