73

Studies on Mental Structures in Children with Neurological Disorders: Part 3 - Development of Visual Perception in Children with Epilepsy and/or Minimal Brain Dysfunction Ryoho Okada, MD, Yoko Hasegawa, MPH and Keizo Tachi, MD Department of Pediatrics, Kanazawa Medical Uni­versity, Ishikawa

Studies on assessment of visual perception in 90 children with epilepsy or minimal brain dysfunction syndrome were carried out with DTVP (Frostig) and WISC. In a large maj ority of the children, the tests were repeated two or three times intermittently at intervals of six to twelve months. Subtests of DTVP were divided into the following five classes: 1) Eye­motor Coordination, 2) figure-ground, 3) constancy of shape, 4) position in space, and 5) spacial relation­ship. On the other hand, spacial scores and conceptual scores were obtained by estimating the scores of WISC subtests. The special score is representative of the function of the right cerebral hemisphere, and the sum of Information, Arithmetic and Digid Span of the verbal subtest score was treated quantitatively as a representative of the whole function of the left cerebral hemisphere. By analyzing the result of DTVP, all children could be classified into the following six types. a) The normal pattern; PQ 100, with a normal distribution of all subtests. b) The mentally subnormal pattern; full IQ less than 69, and diffuse low PQ in all parts. c) The pattern of selective low perception score in the subtest part 1. d), e) and f) The same pattern with (c) but in the subtest part 3 or 4 or in the mixture of the subtests 1 and 3.

Results (1 ) The profile of immature perception in each part developed into higher perceptual levels with age with some modifications in most patients receiving medical treatment. (2) Development of PQ was accompanied by an increase of spacial scores and right hemispheric function, or conceptual scores. (3) The selective im­mature pattern in the subtest part 1 was associated with a large discrepancy between PIQ and PQ. MBD and epilepsy equivalent were observed frequently in this group. (4) The selective immature pattern in the subtest part 3 was associated with low scores in the visual association process of ITPA. Discrepancies of both PIQ-PQ and VIQ-PQ were remarkable. In addi­tion, this pattern was observed in 57% of MBD pa­tients. (5) The selective immature pattern in the su btest part 4 and the mixture part 1 and 3 were high­ly associated with low scores in the auditory sequen­tial memory of ITPA.

Key words: Psychometry, perception, DTVP, epilep­sY,MBD.

74

An Epidemiological Study on Febrile Convul­sions: A Survey in a Health Examination for Children at 3 and a Half Years of Age Hidenori Yamawaki, MD, Tohru Seki, MD, Nobuyuki Suzuki, MD, Satoshi Kimiya, MD, Mariko Maezawa, MD and Makoto Hirose, MD Department of Pediatrics, School of Medicine, Keio University , Tokyo (HY, TS, NS, SK, MM) ; Yokosuka Kyosai Hospital, Yokosuka, Kanagawa (MH)

We investigated some epidemiological aspects of febrile convulsions (FC) in 3-and-a-half-year-old children who attended a health examination at Yoko­suka Chuo Health Center between April 1980 and March 1981, 2,922 children, or 94% of children who reached the age during that period in the central area of Yokosuka City, were examined. Two hundred and sixty-six children out of the 2,922 (8.1%) had a history of FC. We obtained a precise history of the seizUres from their mothers. The results of the study are summarized as follows. 1) As many as 112 cases (42%) had their first attack

between 12 and 23 months of age, 42 cases (18%) under 12 months of age, 61 cases (26%) between 24 and 35 months of age, and 22 cases (9%) be­yond 36 months of age.

2) Thirty-two cases out of the 2,922 (18%) had ex­perienced atypical seizures, which included seizures lasting more than 10 minutes, focal seizures and recurrent seizures within 24 hours.

3) There were no significant difference in prevalence between boys and girls, although boys were slightly more affected than girls.

4) A third of children who experienced FC had at least one recurrence, and a half of those who had had one recurrence had a further attack or attacks.

5) There was a tendency that more febrile seizures occurred in winter and spring. Prolonged seizures also tended to occur more often in those seasons; proportions of prolonged seizures (more than 15 minutes) to all febrile seizures in winter, spring, summer and fall were 6.2%, 8.2%, 2.4% and 0% respectively.

6) The occurrence rate of status epilpicus in febrile seizures were 5.3 per 1,000 seizures.

Key words: Febrile convulsion, health examination, epidemiology.

Brain & Development, Vol 5, No 2, 1983 181

75

Prognosis in Children with Febrile Convulsions Shota Miyake, MD, Kazue Honda, MD. Yukihide Ike, MD and Seiji Kimura, MD Department of Pediatrics, Yokohama City University School of Medicine, Yokohama, Kanagawa

We studied retrospectively the relation between febrile convulsions (FC) and epilepsy (Epi) in children who had experienced FC.

Questionnaires were sent in 1981 to the parents of 215 children with non-treated FC who were selected from 2,788 children who visited our clinic in 1975. And we received 104 answers (non-T-FC). They were compared with 50 children with FC on medication (T-FC), 74 epileptic children with FC in their past history (FC-(+)-Epi) and 80 epileptic children without FC(FC-(-)-Epi). All were over 7 years old. The FC groups were characterized by the larger number of males (M/F = 1.2, 2.1, 1.0, 1.0) and higher incidence of a family history of FC(45%, 38%, 24%, 16%). The incidence of a family history of Epi was without dis­tinction in the four groups. The first FC occurring before 6 months and after 5 years old was equally observed in the non-T-FC(l4%), T-FC(l2%) and FC-(+)-Epi(ll%) groups. FC in the T-FC group con­tinued after 7 years old (16%) and 32% had four or more recurrences, as compared with the non-T-FC (5%,20%) and FC-(+)-Epi (6%,21%) groups.

Continuous AED treatment was successful in preventing subsequent febrile convulsions, as seen in the recurrence rates in the T-FC and FC-(+)-Epi groups, 23% (60% of them had only one attack after treatment) and 5.4%. But 10 cases in the non-T-FC and 5 cases in the T-FC group had afebrile convul­sions. Most of them had several risk factors, especially early onset, positive family history of Epi, frequent at tacks and plural attacks in 24 hours. The onset of Epi of FC-(+)-Epi nearly equaled that of FC-(-)-Epi judging from the age distribution except that the former was seen in a larger number of 3-6 years olds than the latter. Sixty-four percent of FC-(+)-Epi cases developed afebrile convulsions within 4 years after the last FC (20% within 2 years and at the latest 14 years after the last FC). The rate of recurrence was very low and only 5 cases had continued attacks 4 years after treatment.

According to our study, AED treatment prevented subsequent FC but did not always prevent subsequent afebrile convulsions. A few of the non-T-FC group developed psychosocial maladjustment and they had several risk factors also. So we thought that the prophylactic treatment of FC was necessary for patients who had the above mentioned risk factors and several other factors; focal attacks, antecedent cerebral injury and neurological abnormalities. We are con­tinuing these follow-up studies and will report the future outcome of our subjects especially with regard to psychomotor epilepsy which is one of the most intractable epilepsies.

Key words: Febrile convulsions, prognosis, genesis of epilepsy.

182 Brain & Development, Vol 5, No 2, 1983

76

A Clinical and Electroencephalographic Study on Children with Febrile Convulsions and Diffuse Spike-Waves in Comparison with Children with Grand Mal Epilepsies and Diffuse Spike-Waves Takashi Kajitani, MD, Makoto Nakamura, MD and Yoshiaki Kumanomidou, MD Department of P ediatrics, Kawasaki Hospital, Kawa­saki Medical School, Okayama

Electroencephalographic follow-up investigations de­monstrated a diffuse 3-4 cps spike-wave burst as the most frequent pattern of epileptiform EEG abnormalities among children with febrile convulsions. Therefore, in order to clarify the relations of febrile convulsions to childhood epilepsy, the present study was undertaken to compare and contrast the differ­ences between children with febrile convulsions ex­hibiting diffuse spike-waves on EEG and children suffering from grand mal epilepsies and presenting with diffuse spike-waves (primary generalized epi­lepsies).

Patients and Methods Eighty-two children who had febrile convulsions and exhibited diffuse spike-waves at least once in the EEG record were investigated in comparison with 40 epileptic children who had grand mal seizures and showed the same EEG abnormalities and whose age of onset of seizures was under 10 years. We compared the two groups as to the age of onset, seizure fre­quency, family history of convulsive disorders, back­ground activity of the EEG, and frequency and duration of diffu se spike-wave bursts, and the activat­ing effect of hyperventilation, photic stimulation and sleep on diffuse spike-waves.

Results Children with febrile convulsions had lower frequen­cies of seizure than children with graJld mal epilepsies. Diffuse spike-wave bursts occurred very inconstantly in children with febrile convulsions, whereas in epi­leptic children they could already be recognized in only a few or even a single EEG record. There were no significant differences between the two groups in other respects.

Conclusion There were no basic differences between febrile convulsions with diffuse spike-waves and grand mal epilepsies with diffuse spike-waves. There was a difference only with regard to the quantity of the characteristics and their expression. These aspects showed that febrile convulsions were indeed an especially benign and pure genetically determined type of childhood epilepsy.

Key words: Febrile convulsions, diffuse spike-wave burst, primary generalized spi/epsy.

77

Longitudinal Study of Rolandic Discharges Makoto Nakamura, MD and Takashi Kajitani, MD Department of Pediatrics, Kawasaki Hospital, Kawa­saki Medical School, Okayama

Rolandic discharges (RD) are defined as spikes or sharp waves recorded with their maximum amplitudes in the centro-temporal region and often, but with lower amplitudes, in the posterior-frontal and parietal regions and with a normal background activity_

We have found RD in patients with febrile convul­sions as well as benign epilepsy of childhood with RD (BECRD), and stressed a close genetic relationship between febrile convulsions with RD and BECRD.

It is well known that RD have strong age depen­dency between the ages of four and nine. In order to clarify the evolution of RD, we performed a lon­gitudinal clinical and electroencephalographic study on 76 patients (58 patients with BECRD, 18 patients with febrile convulsions) for whom EEG examinations were repeated more than 3 times.

There were 34 males and 24 females with BECRD, and 10 males and 8 females with febrile convulsions­In the BECRD group. 32 cases had generalized sei­zures, probably secondarily generalized seizures with focal onset, 13 cases had partial motor seizures and the other 13 cases had both generalized and partial seizures. In the febrile convlusions group, 17 cases had generalized and only 1 case had partial seizures.

RD began to appear between 2 and 11 years of age (average: 7.8 ± 2.8 years of age) in patients with BECRD, while they began to appear between 1 and 11 years of age (average: 5.5 ± 2.7 years of age) in pa­tients with febrile convulsions.

As a rule RD appeared unilaterally but they also occurred bilaterally from two foci apparently inde­pendent of each other, of which the one with higher amplitudes dominated the other. RD disappeared spontaneously at 10.7 ± 3.7 years of age on average in the BECRD group, while they disappeared at 7.8 ± 2.8 years of age on average in the febrile convul­sions group.

RD could shift sides in two successive recordings or might disappear in one or more recordings, which were entirely normal, to reappear in the subsequent ones.

Bilaterally synchronous 3-4 Hz spike-and-wave activity and RD might appear in the same EEG in both groups, but they appeared more often in the febrile convulsions group than the BECRD one.

Key words: Rolandic discharges, benign epilepsy of childhood with rolandic discharges (BECRD) , febrile convulsions, bilaterally synchronous 3-4 Hz spike-and­wave activity.

78

Clinico-Pharmacological Study on the Optimum Dosage Regimen of Rectal Diazepam Supposi­tories in the Prevention of Recurrence of Febrile Convulsions liro Yagi, MD, Kimio Minagawa, MD and Hisao Miura, MD Department of Pediatrics, Kitasato University School of Medicine, Sagamihara, Kanagawa

In a preliminary study, plasma concentrations of dia­zepam (DZP) and its main metabolite, N-desmethyl­diazepam (N-desmethyl-DZP), were followed for 48 hours after a single rectal administration of DZP (0.5 mg/kg) to infants with febrile convulsions- Two types of preparations were used. Rectal administration of DZP solutions resulted in a rapid increase in plasma concentrations of DZP. Therapeutic plasma levels (above 150 ng/m!) were attained within 10 minutes. DZP suppositories did not give the therapeutic level until 30 minutes after administration. The average time to reach the maximum plasma concentration (CPmax) was delayed significantly compared to that for rectal DZP solutions. However, the therapeutic plasma DZP levels were maintained for a longer period (about 8 hours) after administration of DZP supposi­tories. N-desmethyl-DZP, which has also been con­sidered to have the anticonvulsant effect, appeared in plasma around 1 hour after rectal administration of both DZP preparations. Plasma levels of N-desmethyl­DZP continued to increase up to 48 hours.

Based on these results, the optimum dosage regi­men of rectal DZP suppositories for the prevention of recurrent febrile convulsions was determined.

Subjects and Methods DZP suppositories of 0.5 mg/kg/dose were given twice with an interval of 8 hours to 6 infants with febrile convulsions of 5 to 22 months of age.

Plasma concentrations of DZP and N-desmethyl­DZP were followed closely for 48 hours after the first administration of a DZP suppository.

Results Therapeutic plasma DZP levels were attained within 30 minutes after the first dose. The average CPmax of DZP and the average time to CPmax were 410.0 ± 131.4 ng/ml and 1.13 ± 0.49 hours, respectively. Plasma DZP levels increased again rapidly after the second dose (CPmax: 654.6 ± 148.1 ng/ml, time to CPmax: 1.00 ± 0.50 hours) and were maintained with­in the therapeutic range for 24 hours after the first dose.

Plasma levels of N-desmethyl-DZP continued to increase and exceeded those of DZP at 24 hours after administration of the first dose.

No serious side effects except for transient seda­tion were observed in any of the patients.

Conclusion A DZP suppository (0.5 mg/kg/dose) may be given to a patient twice with an interval of 8 hours when the temperature remains elevated, for the prevention of recurrent febrile convulsions.

Key words: Febrile convulsion, diazepam, N-des­methyldiazepam.

Brain & Development, Val 5, No 2,1983 183

79

Etiologic Factors and Long-Term Prognosis of Convulsive Disorders in the First Year of Life Akiko Matsumoto, MD, Kazuyoshi Watanabe, MD, Midori Sugiura, MD, Tamiko Negoro, MD, Etsuko Takaesu, MD and Katsuhiko Iwase, MD Department of Pediatrics, Nagoya University School of Medicine, Nagoya, Aichi

Etiological factors and long-term prognosis were stu­died in 562 cases with convulsive disorders in the first year of life; 114 (20.3%) was prenatal, 114 (20.3%) perinatal, 24 (4.3%) postnatal, and 257 cases (45.7%) were cryptogenic. The remaining 53 (9.4%) patients were doubtful cases. The mortality before six years of age of the pre- and perinatal cases at 17.6% and 15.7%, respectively, was significantly higher than in the other etiologic groups.

The incidence of a family history of epilepsy or other convulsive disorders was highest in the crypto­genic cases (23.5%), and lowest in the prenatal cases (10.4%) (p < 0.05). The onset of seizures was very early in the pre- and perinatal groups and they de­creased in number after four months of age.

With regard to the seizure types in the fIrst year of life, infantile spasms occurred most frequently as the initial seizures in prenatal (62.8%) and doubtful (50.9%) group, and generalized motor seizures in cryptogenic (78.8%) group. The incidence of positive family history was highest in generalized motor sei­zures (23.7%), lower in infantile spasms (14.2%) and lowest in other secondary generalized epilepsies (2.9%). As to the first paroxysmal EEG, 73.8% of the cryptogenic cases showed no spikes, but only 15.4% of the prenatal group did so.

The prognosis for seizures and mental and physical development was much better in cryptogenic cases. More than 80% of cases with cryptogenic etiology became seizure-free, mentally and physically normal, whereas in other etiologic groups the recovery rate was much lower (3.6-28.6%).

Key words: Etiologic factors, long· term prognosis, convulsive disorders, first·year epilepsy.

184 Brain & Development, Vol 5, No 2,1983

80

Benign Infantile Convulsion and Infantile Diarrhea Hiroko Ogata, MD, Akihisa Mitsudome, MD, Masaharu Ohfu, MD, Hidetoshi Hirano, MD and Katsuichi Irie, MD Department of Pediatrics, School of Medicine, Fuku· oka University, Fukuoka

118 cases of benign infantile convulsion were studied. 56 cases were male and 62 cases were female. Benign infantile convulsion with diarrhea were 47 cases (24 males and 23 females).

Benign infantile convulsions could be classified into three types according to the characteristics of condition; Type A (only one convulsion); Type B (frequent convulsions during few days); Type C (a few convulsions during few months). Most of the pa­tients fell into Type B (62 cases).

The highest incidence was at the age 1-2 years. Cases with diarrhea were with the peak in winter

(November, December, January and February). CSF findings were normal in 21 cases. Rotavirus was identified in 70-80% of children

with diarrhea. Most children infected with rotavirus were under 2 years of age. The prevalence of rotavirus among the diarrhea cases during the coldest months of the year, i.e. November to March, was 70-80%.

The sequelae were composed of speech retardation (6 cases) and epilepsy (8 cases). .

The present study suggests that benign infantile convulsion with diarrhea during winter is related with rotarirus infection.

Key words: Infantile convulsion, infantile diarrhea, Rotavirus.

81

Benign Afebrile Infantile Convulsions As­sociated with Rotavirus Gastroenteritis Atgushi Ona, MD, Kiyoshi Luke Taniuchi, MD and Tateo Sugimoto, MD Taniuchi Children's Hospital, Osaka (AO, KT); Depart­ment of Pediatrics, Kansai Medical University, Mori­guchi, Osaka (TS)

In our hospital, 336 cases of Rotavirus gastroenteritis were observed and 12 of them showed benign afebrile convulsions. We dicussed the etiologies of infantile convulsion by using the examination results in our 12 cases.

Materials and Methods 730 patients with acute gastroenterit is were examined by electron microscopy (EM), culture of stool, and complement fixation (CF) antibody method during 6 years from April, 1975 to March, 1981. Rotavirus was observed in 336 cases of 730 patients (male: 196, female:140; 20 days to 8 years old). Twelve cases of 336 Rotavirus infection showed afebrile convulsions whose ages ranged from 12 to 25 months (male:5, female :7). Epileptic and febrile convulsions were excluded by clinical course and examination. Peri­pheral blood cells, blood sugar, total protein, BUN, and electrolites (Na, K, Cal were measured just after the convulsions. Lumbar punctures were done in 5 cases. Electroencephalograms (EEG) were also ex­amined in 10 cases. All cases were not in the states of severe dehydration.

Results Clinical features: All convulsive cases showed vomit­ing for a few days, which appeared 1 to 3 times a day. Stools were watery and muddy in fonn, and whitish yellow in color. Frequency of defecation was 1 to 6 times a day. The above findings indicated no difference with other non-convulsive patients with Rotavirus infection. Convulsion : Generalized tonic­clonic convulsions appeared within several days of the clinical course. Eight cases repeated convulsions several times for 2 days. In most cases, the duration of a convulsion was within 3 minutes. Laboratory findings : Lumbar puncture, EEG, peripheral blood count, blood sugar, serum electrolites, total protein, and BUN were all within normal range. Virological examination: Rotavirus was detected by EM in the stools of 12 cases and CF antibody to Rotavirus elevated in 5 cases tested. But we could not find any other virus infection by EM and culture of stools.

Discussion Fukuyama [1 J reported infantile convulsion which is "Recurrent but benign generalized convulsions of unknown etiology in infants." We followed the course of our patients for 1 to 4 years, however, any convul­sive attack was not observed. These findings suggest that convulsions induced by Rotavirus infection are infantile benign generalized convulsions.

Reference 1. Fukuyama, Y. Clin Psychiatr (Tokyo) 1963 ;5:211.

Key words: Rotavirus, infantile convulsion, gastro­enteritis.

82

Nervous Diseases in Children Treated as Emer­gency Outpatients Hideshige Mizue, MD and Shigekazu Kuroki, MD Department of Pediatrics, Kobe Municipal Central Hospital, Kobe, Hyogo

The majority of nervous diseases in children occur with sudden convulsions or disturbance of consciou!!­ness, and therefore many youngsters have visited us as emergency outpatients. In the present paper, infor­mation on children with nervous diseases seeking treat­ment at night (from 5:00 pm to 9:00 am) and on holidays as emergency outpatients during the 3-year period from 1979 through 1981 was compiled con­cerning their numbers and the kind of disease, in order to determine the importance of emergency outpatient treatment with regard to children with nervous dis­eases.

The total number of emergency outpatients visit­ing us during the above mentioned 3-year period was 57,658, among whom the number of those visiting the Department of Pediatrics was 27,839, accounting for 48.3% of the total patients. The number of chil­dren with nervous diseases was 1,542, corresponding to 5.5% of infant patients. (The number of these pa­tients showed a tendency to increase from January through March, and to decrease from September through October. This tendency corresponds to the seasonal changes in the occurrence of febrile convul­sions.) The number of patients classified by disease is as follows: febrile convulsions 1,105 (71.6%), epilepsy 143 (9.3%), status epilepticus 63 (4.1 %), other con­vulsive diseases 143 (9.3%), bacterial meningitis 15 (1.0%), aseptic meningitis 14 (0.9%), encephalitis and encephalopathy 14 (0.9%), and others 45 (2.9%). The number of hospitalized emergency outpatients was 133 (8.6%).

The following findings are worthy of note : 1) Interesting diseases including Tay-Sachs disease,

Wilson disease, tuberous sclerosis, moya moya disease and brain tumors may sometimes be found at the emergency outpatient clinic.

2) Seventy-five percent of inpatients with bacterial meningitis, for whom early treatment is important, visited us as emergency outpatients.

3) Patients with status epilepticus must receive prompt treatment to stop convulsions. On the occasion of such patients visiting our emergency outpatient clinic, they are referred to pediatricians for the appropriate treatment. Fron the viewpoint of a physician treating infant

nervous diseases, emergency treatment thereof is most important.

Key words: Emergency treatment, emergency service, bacterial meningitis, febrile convulsion.

Brain & Development, Vol 5, No 2,1983 185

83

Clinico-Electroencephalographic Observations of Grand Mal Epilepsy in Childhood Seizi Kimura, MD, Kazue Honda, MD, Shota Miyake, MD and Yukiyoshi Ike, MD Department of Pediatrics, Yokohama City University School of Medicine, Yokohama, Kanagawa

Grand mal epilepsy (GM) is one of the most frequent disorders in childhood, but there are only a few reports on childhood GM available in Japan. The authors reported on GM in childhood without motor and mental deficits, with regard to the following points. I) Clinico-electroencephalographic differences between the cases with a history of febrile convulsion (Fe) and those without FC. 2) Recurrence rate of seizures after medication. 3) The age when epileptic discharges in EEG disappeared: 4) The disappearance of epileptic discharges due to either the effect of anti­convulsants or the natural course of maturation.

Materials and Methods One hundred and twenty-six infants and children with GM without motor and mental deficits, who had been followed up for four years or more, were divided into two groups. Group A consisted of 88 patients without a history of FC, and group B 38 patients with one. We analyzed the clinico-electroencephalographic data, comparing A with B.

Results 1) There was no difference in the recurrence rate of convulsions between A and B. Sixty-seven cases were seizure-free after the administration of anticonvul­sants, and only one to four percent of the patients showed convulsions who had been followed up for four to ten years under medication. 2) Epileptic dis­charges were found more frequently in group B in the first and the last EEG; 66% (group A) and 76% (group B) in the first EEG, and 22% and 34% in the last. 3) The peak age of the patients having epileptic dis­charges in EEG was seven to eight years as a whole. The epileptic discharges in EEG diminished gradually with age, and occurred in 12% of the patients at the age of 17-18. 4) EEG was improved more often in the group of patients with the onset of convulsions after seven years of age as compared to those before seven years. 5) Focal epileptic discharges in EEG were seen in 88 cases during their clinical course; fixed foci in 47, migrated foci in 23 and multiple foci in 18. Group A showed a higher incidence of migrated epileptic foci than B (statistically not significant). Dominant epilep­tic foci in group A were localized in the central and mid-temporal areas (statistically significant).

Comment In general, childhood grand mal epilepsy without mental and motor deficits showed a good prognosis. There was no clinical difference between groups A and B, but the percentage of patients with epileptic discharges in EEG was slightly higher in group B. The EEG findings described in results (3) and (4) indicate that the brain maturation might play a more im­portant role in the disappearance of epileptic dis­charges in EEG than the effects of anticonvulsants.

186 Brain & Development, Vol 5, No 2, 1983

Key words: Childhood, grand mal epilepsy, epileptic discharge.

84

A Clinical Study of 205 Photosensitive Epilep­tic Patients Tateki Fujiwara, MD, Kazuichi Yagi, MD and Masa­kazu Seino, MD Shizuoka Higashi Hospital, Shizuoka

Two hundred and five patients with photoconvulsive responses, ranging from 2 to 64 years of age, were the su bjects of this study. The rate of occurrence of photosensitive epilepsy with respect to the type of epilepsies in a 6,634 cohort population was: 5.5% in primary generalized, 5.4% in secondary generalized, 3.4% in undetermined generalized, 0.8% in partial and 3.4% in unclassified epilepsy.

According to the Bickford classification (1953), we divided the patients into three groups; 16 patients with environmentally produced photic seizures (group A), 31 with seizures induced by photic stimulation only in the laboratory (group B) and 158 with photic­induced paroxysmal discharges without clinical seizures (group C). Intelligence deficiency of various degrees was observed in all of group A (16/16),61% (19/31) of group Band 39% (62/158) of group C.

There were 84 patients with secondary generalized epilepsies : 33 with Lennox-Gastaut syndrome, 13 with myoclonus epilepsy and the remaining 38 with secondary generalized epilepsy which, however, failed to fulfill the conventional syndromic criteria. At least 27 out of these 38 patients were characterized by, but not always, combined seizures of myoclonic absence, myoclonic jerks and generalized tonic-clonic convul­sion. They were tentatively classified as photosensitive myoclonic epilepsy (PME).

The common features of PME were: mental re­tardation without exception, a positive past history (12/27, 44%) but no family history of epilepsy, onset of epileptic seizures prior to 3 years (22/27,82%) and an obvious tendency toward resistance to therapy. EEGs were characterized by background activity with slow waves and short bursts of irregular spike-waves mostly faster than 3 c/sec. Clinical seizures induced by photic stimulation were present in 59% (16/27), which were in either group A or B. PME is supposed to be a syndromic entity closely related to severe myoclonic epilepsy proposed by Dravet et al in 1981.

The overall incidence of photosensitive epilepsy was almost the same between primary and secondary generalized epilepsies. However, clinical seizures induced by photic stimulation were most frequently found in those with secondary generalized epilepsy. Among them, a group of patients with conspicuous photosensitivity was proposed to be photosensitive myoclonic epilepsy. The dissimilarity of clinical fea­tures was discussed in comparison with those of Lennox-Gastaut syndrome.

Key words: Photosensitive myoclonic epilepsy, sei­zures induced by photic stimulation, photoconvulsive response.

85

Unilateral or Predominantly Unilateral Seizures - Their Clinical Course, Electroencephalogra­phy, Computed Tomography and Prognosis­Satoshi Kimiya, MD, Tohru Seki, MD, Hidenori Yama­waki, MD, Nobuyuki Suzuki, MD and Mariko Mae­zawa, MD Department of Pediatrics, School of Medicine, Keio University, Tokyo

Unilateral or predominantly unilateral seizures were eliminated from the international classification of 1979. We studied their clinical course, electroen­cephalography, computed tomography and prognosis.

Considering their clinical and pathophysiological peculialities, we propose that they should be classified as one seizure type.

The diagnosis was made according to the following criteria.

Convulsions which are characterised by the clonic tonic or tonic-clonic type, with or without impairment of consciousness, and expressed only or predominant­lyon one side.

Results 1) Possible causes: Perinatal, 9%; prenatal, 18%

(Sturge-Weber syndrome, Recklinghausen, etc); postnatal, 18% (meningitis, encephalitis, head trauma, etc); and unknown, 55%.

2) EEG (paroxysmal abnormalities): Diffuse spike and wave, 15 cases; focal spike and wave, 4 cases; focal spike, 18 cases; and none, 12 cases.

3) Cranial computed tomography (27 cases): Normal, 12 cases; abnormal, 15 cases (diffuse, 8; focal,S; diffuse + focal, 2.)

4) Courses before this unilateral seizure: Type 1, began with unilateral seizures, 33 cases; Type 2, began with grand mal, febrile convulsions, 10 cases; and Type 3, began with other types, 2 cases.

5) Follow-up of 39 cases for longer than 2 years: Convulsions disappeared, 30 cases; and convulsions continued, 9 cases. Eleven cases changed to such seizure types as

atypical absence, myoclonic seizure infantile spasms, etc.

Key words: Unilateral seizures, convulsions, EEG, CT.

86

Ten Year Follow-Up Study of 272 Epileptic Children Isamu Tarnai, MD, Hideomi Ohta, MD, Tadao Takei, MD and Kihei Maekawa, MD Department of Pediatric Neurology, Saitama Chilo dren's Medical Center, Iwatsuki, Saitama (IT): Depart­ment of Pediatrics, Sagamihara National Hospital, Sagamihara, Kanagawa (HO, TT); Department of Pediatrics, The Jikei University School of Medicine, Tokyo (KM)

Of 808 epileptic children first seen before December 1971,272 were followed for more than 10 years (aver­age 13.9 years) by electroencephalography (EEG). We investigated the course of epilepsy and the adapta­tion to social life in these cases.

1) The course of EEG: The changes of EEG findings were classified as follows. A: bilateral spikes at the first EEG which disappeared after anticonvulsant therapy. A*: bilateral spikes at first which persisted during therapy. B* or B: The course of focal spikes at first which persisted or disappeared thereafter. C* or C: bilateral spikes changing into focal spikes in the course of therapy which persisted or disappear­ed thereafter. D* or D: no spikes in the initial EEG, followed by the appearance of spikes discharges which persisted or disappeared thereafter. E: no spikes dur­ing the whole course of therapy. The numbers of cases with each seizure type were summarized as (A * / A, B*/B,C*/C,D*/D,E). Grand mal (G) (14/16,27/26, 21/12,24/29,12), psychomotor seizures (P) (0/0,4/3, 0/0,0/3,0), focal seizures (F) (0/0,12/6,6/0,1/1,0), in­fantile spasms (I) or Lennox Gastaut syndrome (L) (11/0,0/0,3/1,0/0,0), myoclonic seizures (M) (7/0, 0/0,3/0,1/0,0), complex absence (C) (4/1,0/0,6/2, 1/0,0), pure absence (A) (0/2,0/0,0/0,0/0,0) and auto­nomic seizures (0) (0/0,1/1,3/1,1/0,6).

2) The numbers of patients who had seizures dur­ing the past one year. G: 10 cases (5.5%), I or L: 5 cases (33.3%), M: 5 cases (45.5%) and F: 4 cases (15.4%).

3) The school career was low in cases with I or L. Forty-nine of 164 cases over 18 years of age entered college or university.

4) Eighty-four have been employed, but many cases with I or L are not working.

5) Five cases out of 18 cases holding a driver's license had seizures during the past two years.

6) There were 7 cases who were admitted to men­tal hospital with psychiatric diseases.

7) Sixteen patients (3 males and 13 females) who got married did not tell their spouses about their epilepsy until the time of marriage. All 12 children of these married couples were healthy.

Conclusion The same pediatric neurologist should treat as often as possible epileptic children until they reach adulthood and should watch they lead a happy life.

Key words: Ten-year follow-up, 272 epileptic chil­dren, school career, driver's license, marriage.

Brain & Development, Vol 5, No 2,1983 187

87

Recurrence of Seizures after Long-Term Remis­sion in Childhood Epilepsy: With Special Reference to Criteria on Discontinuance of Antiepileptic Medication Mariko Maezawa, MD, Tohru Seki, MD, Hidenori Yamawaki, MD, Nobuyuki Suzuki, MD and Satoshi Kimiya,MD Department of Pediatrics, School of Medicine, Keio University, Tokyo

There are no general conceptions of discontinuation of antiepileptics, and we need a practical guideline. We investigated the prognosis of 52 cases of epileptic children. In this study, we were concerned with re­lapses and factors influencing prognosis about infan­tile spasms, absence seizures, myoclonic seizures and complex partial seizures.

Methods Sixty children were chosen for this study, who had had no seizures for five years. They were followed in our outpatient clinic since January, 1965. The sub­jects were divided into two groups as follows; the follow-up group (52 cases), and the drop-out group (8 cases). In this report, we studied only the follow-up group. The main seizure types were infantile spasms (12 cases), absence seizures (23), myoclonic seizures (4) and complex partial seizures (13). .

Results Relapse was found in 3 of 12 infantile spasms patients who were followed for 5 years and 2 months to 15 years and 4 months. These 3 cases were characterized by (1) mental retardation prior to the onset of infantile spasms, (2) the slightly higher ages at which infantile spasms ceased, (3) retarded develop­ment, (4) known organic causes, and (5) EEG ab­normalities.

All absence seizures remained free of fits for 5-14 years. Of the 4 patients of myoclonic seizures, only one case had seizures after the seizure-free period of 5 years and 6 months. He took drugs irregularly by himself.

As a whole more relapses occurred among those with (1) persi;tent or nonpersistent EEG abnormali­ties, (2) retarded development, and (3) remarkable organic causes.

It seems reasonable to make a guideline of dis­continuation of antiepileptics according to the type of seizures. We should also be cautious with age, sex, and environment of patients.

Key words: Childhood epilepsy, recu"ence, discon­tinuation of antiepileptics.

188 Brain & Development, Vol 5, No 2,1983

88

A Study on the Personality of Epileptic Chil­dren Hitomi Sato, MD and Katsuji Nakamura, MD Faculty of Education for Handicapped Children, Shiga University, Shiga (HS); Pediatric Clinic, Fukui Red Cross Hospital, Fukui (KN)

It is important to consider emotional and behavioral disorders as well as seizure control in epileptic chil­dren. This study was undertaken in order to clarify personalities of epileptic children and the relationship to seizure control, EEG abnormalities and seizure types.

Subjects and Methods Ninety epileptic children, who had been treated with anticonvulsants for more than three years, were examined by the Y -G personality test. Sixty percent of them have had grand mal or secondarily generalized seizures.

Results Twenty of the 90 children (22.2%) showed typical personality profiles, 1 the average type (A), 5 the blast type (B), 5 the calm type (C), 4 the director type (D) and 5 the escape type (E). When subtypes were included, 32 of the 90 children showed the blast type or escape type. But there was no significant relation between these two types and seizure control or EEG abnormalities. The 90 were divided into 3 groups (elementary school, junior high school, senior high school). And the disparity in each factor (D, C, I, N, 0, Co, Ag, G, R, T, A, S) between each group of epileptic children and control group was assessed. In boys and girls of the elementary school group, G (general activity), T (thinking introversion), and R (rhathmia) were significantly different from the control group. In junior high school boys, only G (general activity) was significantly different from the control group. In senior high school, none of the factors was significantly different from the control group.

As for factor analysis, two factors were sampled from 12 factors; Factor 1, emotional instability (D, C, I N ° Co Ag) and Factor 2, social unfittness (G, R, i, A, S). Analysis of these two factors showed that the senior high school group showed a significant dif­ference of Factor 1 (emotional instability) in seizure control and EEG findings.

Key words: Y-G personality test, epilepsy, EEG, seizure control.

89

Clinical Studies of Infantile Spasms with Cerebral Palsy Kaoru Konishi, MD, Akira Tamamoto, MD, Katsuyo Hashimoto, MD, Yukuo Konishi, MD and Kiyoshi Takaya, MD Department of Pediatrics, Kisshoin Hospital, Kyoto (KK, AT, KH); Kyoto University, Kyoto (YK); Biwakogakuen, Ohtsu, Shiga, (KT).

Infantile spasms represent an age-dependent epilepsy with various etiological factors. It is well known that infantile spasms often occur in infants with cerebral palsy. Since there have been few studies of the clinical features of infantile spasms in cerebral palsy, we report here the characteristic features of this disorder.

Materials and Methods The subjects were 22 children with infantile spasms and cerebral palsy (14 males, 8 females) who visited our hospital from 1973 to 1980, and 21 other children (13 males, 8 females) with infantile spasms but no cerebral palsy who visited our hospital from 1975 to 1981. The etiological factors, age of onset, type of seizures and prognosis were analyzed. Electroen­cephalograms and CT scans were performed in all cases. All patients were treated with ACTH as soon as possible.

Results In comparison with infantile spasms without cerebral palsy, the characteristics of infantile spasms in patients with cerebral palsy were: 1) A much higher incidence of perinatal problems,

especially severe asphyxia and neonatal convul­sions.

2) Seizures occurred from 1 to 4 months after birth in about 60% of cases.

3) Abnormal eye movements such as deviation, fixation, sunset-like movement and nystagmus were observed in most cases.

4) CT scans revealed severe brain atrophy. 5) After ACTH therapy, focal spikes or spike-waves

persisted in all cases.

Discussion Our studies suggest that infantile spasms in patients with cerebral palsy are induced by more severe brain damage than in those without cerebral palsy. The onset of seizures was earlier. Abnormal eye movement was an important finding to predict the occurrence of infantile spasms. It is necessary for a good prognosis to detect the onset of attacks of infantile spasms early and to treat them adequately.

Key words: Infantile spasms, cerebral palsy, abnormal eye movement.

90

A Clinical Study of the Perinatal Course of Six Cases with Infantile Spasms in Comparison with 24 Other Neonates with Hypoxic-Ischemic Encephalopathy Kitami Hayashi, MD, Tadashi Kawakami, MD, Mitsu­hiko Takata, MD, Hiroshi Akamatsu, MD and Seijiro Aso,MD Departments of Prematures and Neonates (KH, TK, MT, HA), Pediatrics (SA), Japanese Red Cross Medical Center, Tokyo

Hypoxic-ischemic encephalopathy (HIE) is the major cause of infantile spasms. We studied the clinical course of neonates with HIE and the predictable factors of infantile spasms.

Materials and Methods Thirty mature neonates were admitted to the Japanese Red Cross Medical Center because of asphyxia and neonatal seizures from January 1979 through Decem­ber 1980 and followed up for at least 12 months. Some perinatal neurological findings of cases with infantile spasms were compared to those of other neonates with HIE.

Results As to the neurological outcome, we classified normal and borderline cases into G-l (16), handicapped cases into G-2 (8), and infantile spasm cases into G-3 (6). Maternal and delivery complications were not sig­nificant as well as 1 minute Apgar scores. All cases suffered from seizures in the first 2 days of life. But they persisted for 3 days or more in G-2 and G-3, whereas they ceased within 2 days in most G-l cases. There were no differences between G-2 and G-3 in terms of duration, severity, and type of seizure. All cases showed poor activity, hypotonus or absence of the Moro reflex in the acute phase. The G-l cases recovered to the normal state in 4 weeks. But ab­normalities persisted in the G-2 and G-3 cases. Some cases of each group showed apneic spells. The G-l group recovered spontaneously or easily on tapping. But the G-2 and G-3 cases could not recover spon­taneously and needed supportive ventilation. The G-l group could feed orally within 14 days of life, whereas most G-2 and G-3 cases could feed only after 14 days. Abnormal eye signs were found in each group. Intra­ventricular hemorrhage (IVH) was found in one G-2 case, and in 3 G-3 cases, but none in G-1.

Conclusions Intractable .seizures, severe apnea, persistence of neurological abnormalities, difficulty in oral feeding, and IVH predicted a poor prognosis for neonates with HIE. IVH was found in infantile spasms more fre­quently than in G-2. But it was not significant. We could not find any specific predictors for infantile spasms.

Key words: Infantile spasms, hypoxic-ischemic en· cephalopathy, intra-ventricular hemorrhage.

Brain & Development, Vol 5, No 2, 1983 189

91

Developmental Assessment of Infantile Spasms Atsumaro Chikusa, MA, Akira Tamamoto, MD, Kaoru Konishi, MD, Katsuyo Hashimoto, MD, Hozumi Araki, MA and Kiyoshi Takaya, MD Department of Pediatrics, Kisshoin Hospital, Kyoto (AC, AT, KK, KH); St. Agnes Junior College for Women, Kyoto (HA); Department of Pediatrics, Biwako Gakuen Hospital, Otsu, Shiga (KT)

In the majority of studies on the long-term progno­sis of infantile spasms, developmental assessment has been made on the basis of DQ (developmental quotient) or IQ (intelligence quotient) rather than DA (developmental age) or MA (mental age). The effect of ACTH therapy on 22 patients in the cryptogenic group was studied on the basis o~ DQ and DA.

The 22 patients were divided into three groups. Group 1: the seizures disappeared with the first ACTH therapy, and further seizures did not recur (7 patients). Group 2: further seizures recurred after the first ACTH therapy, but the second ACTH therapy was not given (3 patients). Group 3: ACTH therapy was given more than twice (12 patients).

In group 1, developmental assessment through DQ differed little from that through DA. In group 2 and group 3, on developmental assessment through DQ, the effect of ACTH therapy was regarded as little. While, on developmental assessment through DA, there is not the least effect.

From the results, it was suggested that long-term prognosis of infantile spasms with developmental retardation should be studied on the basis of DA continuously.

Key words: Infantile spasms, development, ACTH.

190 Brain & Development, Vol 5, No 2,1983

92

Neuropsychological and Electroencephalogra­phic Study on the West Syndrome and the Lennox Syndrome Naofumi Ichiba, MD, Yasuko Yamatogi, MD and Shunsuke Ohtahara, MD Department of Pediatrics, and Developmental Neuro­science and Child Neurology, Okayama University Medical School, Okayama

Neuropsychological and electroencephalographic study was performed to clarify the mechanism of mental deterioration of the West syndrome and the Lennox syndrome.

Forty-six epileptic children com prizing 33 children with Lennox syndrome and 13 children with West syndrome (group I), aged 4 to 15 years, and 40 non­epileptic children with mental retardation (group 11), aged 5 to 11 years were examined. In addition to the EEG studies, following neuropsychological studies were performed: 1) lateral dominance of hand, foot and eye, 2) intelligence test, 3) Illinois test of psy­cholinguistic abilities (ITPA) (Japanese edition) and 4) Bender Gestalt test.

The results were as follows: 1) Intelligence Quo­tients (lQ) of 16 patients in group I were above 90, IQ of 9 patients in group I and 17 patients in group II were between 76 and 89, and IQ of 21 patients in group I and 23 patients in group II were below 75. 2) Evaluation of 10 subtests in ITPA revealed that a patchy defect was found in association function in both groups (50.0% in group II and 45.0% in group II). But their contents of disorder in association func­tion were different between two groups, that is, although disorder of association function in group II was always in auditory association function, that in group I was mainly visual association function in ad­dition to auditory association function. There was high correlation between disorder of association func­tion and school performance. 3) In Bender-Gestalt test (Koppitz's method) 23 cases of 42 in group I and 22 cases of 35 in group II had a high score beyond normal range. 4) In investigation of EEG study all cases of both group showed abnormalities of basic pattern. The incidence of seizure discharge in group II was 51.3% and the seizure discharge had disappear­ed in 8 cases of 46 in group I at present. The patients with Lennox syndrome who had unlocalized cerebral seizures on EEG showed more frequently disorder of association function than the patients who had focal cortical seizures, but there was no correlation between disorder of association function and continuation of epileptic attacks. The incidence of prolongation of the latency in visual evoked potential was higher in group I (24.3%) than in group II (14.3%).

These findings suggested that the disorder of visual association function which was scarcely found in mental retardation was. characteristic of mental de­terioration in the West syndrome and the Lennox syndrome.

Key words: Mental deterioration, West syndrome, Lennox syndrome, neuropsychological study, EEG.

93

Polygraphic Study during Sleep in West Syn­drome Yoshihide Iwakawa, MD, Toshihiro Niwa, MD, Masa­katsu Ogiso, MD, Masayasu Ota, MD, Shigeri Hosaka, MD and Masaya Segawa, MD Department of Pediatrics, School of Medicine, Tokyo Medical and Dental University, Tokyo (Y!, TN, MO, MO, SH); Segawa Neurological Clinic for Children, Tokyo (MS)

In West syndrome, the brainstem fUnction is thought to be disturbed. The neurons of the brainstem play an important role in regulating sleep and its parameters. In order to clarify the importance of the dysfunction of the brains tern in West syndrome, polysomnographi­cal examinations were performed and the findings were assessed with the prognosis. Five West syndrome cases were subjected to this study. They were divided into two groups according to their prognosis. Group 1 showed relatively good prognosis. Seizures were easily controllable and have not occurred for more than 12 months. In group 2, seizures were intractable and were uncontrollable by medication. In 5 normal children ranging in age from 7 months to 10 years the same studies were performed.

Recordings were performed on two consecutive nights and the second night recordings were used for analysis. The polysomnography consisted of EEG from C4 and P4, bipolar EOG from electrodes attached to the outer canthus, and surface EMG from submental muscle and 5 or 6 other muscles including those of trunk and limbs. Sleep stages were determined at each minute according to the APSS standard. Body move­ments were classified into two types on the basis of their distribution over the body and on their dura­tion. Gross movements (GM) involved the body trunk and lasted for more than two seconds. Twitch move­ments (TM) were located in one muscle on surface EMG recordings lasting less than 0.5 seconds.

Results: In normal children and group 1 the rates of body movements (GM, TM) in sleep 1 and REM are significantly higher than in slow wave sleep. The pattern of twitch movements is the same in all mus­cles. On the contrary, in group 2, there was no correla­tion between the frequency of body movements and sleep stages.

Cases of hereditary progressive dystonia with diurnal fluctuation show a low frequency of body movements during sleep which don't correlate with sleep stages. With administration of L-DOPA, symp­toms of these patients such as dystonia disappear and the pattern of body movements during sleep improves.

These facts suggest that body movements during sleep are related to the catecholaminergic system. Therefore our data indicate, that the prognosis of West syndrome may depend on the catecholaminergic sys­tem.

Key words: West syndrome, polygraphic sleep study, catecholaminerfdc system.

94

A Peculiar High Density Area on CT Scanning in an Infant with Hydrocephalus and Infantile Spasms Yasuko Hasegawa, MD, Tohru Ikuse, MD, Yoshimasa Abe, MD, Teruaki Tamagawa, MD, Eiji Kurihara, MD and Kazuhiko Komiya, MD Department of Pediatrics (YH, TI, YA), Neurosurgery (TT) , Kyorin University, School of Medicine, Mitaka, Tokyo; Tokyo Metropolitan Hospital of Neurology, Fuchu, Tokyo (EK, KK)

Intracranial calcification is known to develop through many conditions, but that primarily developing in the white matter is very rare.

Case Report A two month-old-boy was admitted because of con­vulsive myoclonic movement of the left eyelid. He was born through cesarian section because of CPO without asphyxia.

His convulsion changed to clonic generalized or left hemi-convulsion and resisted medication.

At 5 months of age hydrocephalus developed, and a V-P shunt was done. After the operation, he suffered from purulent meningitis, which was treated with antibiotics. Epileptic seizures changed to infan­tile spasms with modified hypsarrhythmia. At 11 months of age ACTH was used with remarkable effect, but myoclonic convulsion relapsed after 2 months.

The CT scan which was almost normal at 2 months of age (the left frontal area was slightly radiolucent), showed ventricular enlargement and a high density area at the left frontal area at 5 months of age. After then, at the white matter of the left hemisphere (main­ly at the frontal area), the density of the CT scan be­came progressively high which was not enhanced by contrast medium. He is now 18 months old and can­not sit alone.

Discussion The characteristics of the present case are; a high density area is unilateral and progressively developing. It seems that the high density area is located on the white matter, which has a curve linear appearance like a U-fiber. The family history of pregnancy is non contributory. His clinical symptoms are; delayed development, epilepsia (infantile spasms), and hydro­cephalus. The CT appearance of this case resembles some cases of Sturge-Weber disease, but the present case has no skin or ocular symptoms. And enhance­ment of the high density area of this case is negative.

From these symptoms and history, no known basic disease was detected.

Key words: CT scan, white matter, calcification.

Brain & Development, Vol 5, No 2, 1983 191

95

Neuropathological Studies of Infantile Spasms Kenkichi Kataoka, MD, Yoshihiro Nakagawa, MDand Hiroatsu Hojo, MD Department of Pediatric Neurology, Shizuoka Prefec· tural Children's Hospital, Shizuoka

Neuropathological studies of infantile spasms were performed on three autopsied cases. The findings in our cases suggest that pathological changes were dominantly present in the cerebral cortex and white matter.

Case 1. Male, born in April, 1977. Died at the age of 2 years and 8 months.

Clinical summary: Birth weight 2,780 g. He showed poor sucking during the neonatal period. He had syndactyly between the 3rd and 4th fingers on the right hand and severe congenital stridor. At the age of 3 months, he developed convulsive attacks and was treated with ACTH. Then he had several episodes of gastric bleeding after nasogastric tube feeding and died of acute bronchopneumonia.

Brain autopsy: Brain weight 826 g. The brain was slightly atrophic. Diffuse vesicular degenerations (microcavitations) were obvious in the cerebral cortex and the number of nerve cells was decreased. Micro­mineralizations (calcifications) were present in a part of the cerebral white matter.

Case 2. Female, born in January, 1980. Died at the age of I year and 3 months.

Clinical summary: Birth weight 2,040 g. She show­ed poor sucking from birth and gained weight poorly. Pigmentary degeneration of the retina was noted at birth. At 5 months of age, she developed massive myoclonic seizures and was treated with anticonvul­sants. The myoclonic seizures diminished in frequency for a few months but relapsed again at the age of 9 months. She was admitted to our hospital at the age of 14 months. During the period of ACTH therapy, she developed severe pneumonia and died suddenly.

Brain autopsy: Brain weight 336 g. Microgyria and microcephaly were present. The cells of the granular layer in the cerebellum were diminished in number, whereas Purkinje cells and basket cells were present normally. Retinal atrophy was also present.

Case 3. Female, born in September, 1979. Died at the age of 8 months.

Clinical summary: Birth weight 2,370 g. Partial asphyxia and apneic attacks occurred during the neonatal period. At one month of age, she develQped general convulsions. At 4 months of age, she devel­oped massive myoclonic seizures and was treated with ACTH. She died of acute respiratory disease and dehydration at the age of 8 months.

Brain autopsy: Brain weight 372 g. Microgyria and microcephaly were present. Periventricular gliosis of the cerebral white matter and tube-like remnants of the ependymal cells were impressive.

Key words: Infantile spasm, autopsy, neuropathology.

192 Brain & Development, Vol 5, No 2,1983

96

Reevaluation of ACTH Therapy for Infantile Spasms Masatoshi Ito, MD, Takehiko Okuno, MD, Tatsuo Takao, MD, Shozo Nakano, MD, Mieko Yoshioka, MD and Haruki Mikawa, MD Department of Pediatrics, Kyoto University, Kyoto

Recently, it has been found that ACTH may induce apparent cerebral atrophy on CT. Most of cases are reversible, but in some cases, subdural effusion occurs or the recovery of "cerebral atrophy" is delayed. It is an important problem whether this "cerebral atro­phy" may influence the development of the patients. To establish adequate administration, we studied the relationship between the doses of ACTH and the "cerebral atrophy", and the effects on seizures or EEGs.

Subjects were 32 cases with infantile spasms ranging from 2 months to 1 year 11 months old. Pre­sumptive causes were prenatal in 11 cases, perinatal in 10 cases, post natal in one case and idiopathic in 10 cases. In 15 cases, ACTH was administered 0.5 mg for children over one year old and 0.25 mg for infants under one year old (full dose) daily injection for 2 weeks, once every other day for 2 weeks, and then twice a week until the number of injections reached 30. In 13 cases, the doses were 0.25 mg for children over one year old and 0.125 mg for infants under one year old (half dose). In four cases, ACTH was adminis­tered 0.01 mg/kg according to the same schedule. CT examinations were performed before, during and after ACTH therapy. Using IVC-10A, both the areas of the intracranial space and that of brain parenchyma in the level which showed anterior horn were measured, and the ratios of occupation of brain parenchyma were calculated.

In four cases, the recovery of "cerebral atrophy" was delayed at the time of 4 months to 6 months after ACTH therapy. Ventricular dilatation tended to remain compared with cortical atrophy. Three of four cases, total doses of ACTH (mg/kg) were above 1.0 mg/kg.

% decrease of brain parenchyma were well cor­related to total dose of ACTH until CT examinations. So, it was considered that total dose of ACTH should be decreased as much as possible.

Between full dose group and half dose group, there was no difference in the effects on seizures or EEGs. However, in the group which administered 0.01 mg/kg/day of ACTH, the effect on seizures or EEGs were not so good compared with that of the full or half dose group. It was suggested that daily dose of ACTH was sufficient from 0.015 mg/kg to 0.025 mg/kg.

Key words: ACTH, computed tomography, cerebral atrophy, infantile spasms. .

97

High-Dose Vitamin B6 Therapy in Infantile Spasms-The Effect and Adverse Reactions Michihito Nakazawa, MD, Tadataka Matsui, MD, Hiroe Takeda, MD, Masaki Miwa, MD, Sumiyoshi Yokoyama, MD, Soichi Kodama, MD and Tamotsu Matsuo, MD Department of Pediatrics, School of Medicine, Kobe University, Kobe, Hyogo

High-dose vitamin B6 therapy was given to patients with infantile spasms or it's sequelae. Twelve cases were initially treated and seven relapsed or were re­sistant to ACTH therapy, five of the latter were diagnosed as Lennox-Gastaut syndrome subsequently. The age at onset for the initial treatment group ranged from one month to seven months and at treatment from three months to twelve months, and for the relapsed or resistant to ACTH therapy group, from four months to two years and one year and five months to thirteen years, respectively. Patients were subclassified into three groups, a) cryptogenic (no obvious etiology without developmental delay at onset,S cases), b) unknown (no obvious etiology with developmental delay, 6 cases) and c) symptomatic (obvious etiology with or without developmental delay: Tuberous sclerosis, 2 cases; hydrocephalus, I; congenital anomalies, 1; intracranial bleeding, 1; neonatal hypoglycemia, 2 ; and asphYXia, 1). Pyridoxal phosphate (20-50 mg/kg) was administered orally, divided into two or three doses.

Complete relief was obtained in three cases, two cryptogenic and one sequelae of intracranial bleeding due to infantile vitamin K deficiency. VPA was added for two owing to less improvement of EEG. Transient relief was obtained in six cases and marked reduction of seizures and improvement of EEG in one case, three cryptogenic, one unknown and three of symp­tomatic etiology. The time between the start and response to this therapy ranged from two to fourteen days, and that between the response and relapse from eight to thirty days. All the five cryptogenic etiology cases obtained complete or transient relief of seizures.

Side effects were observed in six cases, elevated transaminases (6 cases), nausea and vomiting (2 cases) and lethargy (1 case). The degree of elevated trans­aminases was as follows: 45-200 IV/ml, 3 cases; 200-500, 1 case; and over 500, 1 case.

A four-month-old infant with hypermethioninemia with respiratory insufficiency · and hepatic failure subsequent to high-dose vitamin B6 therapy was re­ported. Pyridoxal phosphate (100 mg/kg) was ad­ministered as a treatment for the hypermethioninemia. One week later, elevated serum transarninases and CO2 narcosis which required mechanical ventilation for four days occurred.

Key words: Infantile spasms, pyridoxal phosphate, anti-convulsant, adverse reaction_

98

Intravenous Gammaglobulin Therapy for Child­hood Epilepsy Motomizu Ariizumi, MD, Shuichi Hibio, MD, Kimio Ogawa, MD, Yutaka Suzuki, MD, Kazuhiko Go to, MD, Osami Okubo, MD, Yasufumi Utsumi, MD and Kazuo Baba, MD Department of Pediatrics, School of Medicine, Nihon University, Tokyo

The experimental models of epilepsy are not only produced by brain tissue damage, pharmacological agents or electrical stimulation, but also autoimmune mechanisms. In clinical studies an immunological mechanism of epilepsy has been revived and a gamma­globulin therapy for some epileptics has recently been mentioned to be effective. Although the mechanism of gammaglobulin action is poorly understood, we tried to assess an effect on early treatment of infantile epilepsy with intravenous nontreated gammaglobulin.

Materials and Methods Eight patients (West syndrome 2, myoclonic seizure 3, Lennox syndrome 1, and focal seizure 2) suffering from the attacks for 2 years and below (group A) and 8 patients (West syndrome 1, myoclonic seizure 4, and Lennox syndrome 3) suffering from the attacks for 2 years or more (group B) received, at 2 or 3 weeks intervals, 100-200 mg/kg body weight of non­treated gammaglobulin intravenously. The effects were assessed according to the frequency and severity of clinical seizures and EEG tracings recorded every 2 to 3 weeks.

Results Four patients (2 each of West syndrome and myo­clonic seizure) of group A came to be free from the attacks in accordance with normalized EEG without anticonvulsants and the other two patients (one each of Lennox syndrome and myoclonic seizure) showed a marked improvement of clinical seizures in agree­ment with EEG improvement. In group B only three patients with Lennox syndrome showed slight im­provement of both clinical and electrical seizures.' All the patients with clinical and EEG improvement showed an increase in serum IgA of over 50% of the pre-treatment level while it was below 30% in the non-improved patients.

Conclusion The intravenous non-treated gammaglobulin therapy in an early stage of infantile epilepsy appeared to be effective. The increase of serum IgA of over 50% of the pre-treatment level may be indicative of the efficacy of this therapy.

Key words: Epilepsy, West syndrome, Lennox syn­drome, myoclonic seizure, gammaglobulin therapy, serum IgA.

Brain & Development, Vol 5, No 2,1983 193

99

Epileptic Encephalopathy with an Unusual Form of Acquired Speech Disturbance Treated with ACTH-Z Kazuyo Inokuma, MD, Kazuyoshi Watanabe, MD, Tamiko Negoro, MD, Midori Sugiura, MD and Akiko Matsumoto, MD Department of Pediatrics, Nagoya University School of Medicine, Nagoya, Aichi

The purpose of this report is to present two cases of children with acquired expressive speech disturbance associated -with paroxysmal EEG abnormalities, which was successfully treated with ACTH-Z.

Case 1 This 6-year-old right-handed boy had a brief gener­alized convulsion at 3.5 years of age. At 4 years his speech became nonfluent but his verbal comprehen­sion was not impaired. EEG showed frequent spike and wave discharges maximally in the right midtem­poral region with transmission to the other areas of the right hemisphere. Close inspection of the patient disclosed fine irregular fasciculation like contraction of the perioral muscle. In NREM sleep, EEG showed nearly continuous and generalized spike and wave discharges more marked in the right hemisphere, which were markedly diminished in REM sleep . Con­ventional anticonvulsant therapy was not effective, but ACTH-Z produced a dramatic improvement in the speech disorder with concomitant disappearance of paroxysmal EEG abnormalities. But the EEG abnormalities and speech disturbance appeared about one month later. Repetitive small spikes appeared first in the mid-temporal area, which increased gradually in amplitUde.

Case 2 This 6-year-old right-handed boy had several convul­sions with fever before 5 years of age, when his speech began to deteriorate and become slurred but not agrammatical. Comprehension of spoken language was spared . EEG showed the same abnormalities as in Case 1. He was successfully treated with ACTH-Z too.

Discussion The etiology of this condition is unknown . This entity is different from absence status. In our two patients, the degree of speech disturbance parallelled the EEG abnormalities. Clinical improvement was associated with disappearance of EEG paroxysmus. Persistent focal EEG abnormalities may be the cause of speech disturbance especially in Case 1, and dysfunction of oral muscle movement might be caused by focal electrical seizures involving the Rolandic motor area. And not only cortical but also subcortical dysfunc­tion might be involved in this condition. The age of onset of the language disorder was the same in both cases, suggesting the same developing factor in the pathogenesis of this disorder. It is also interesting that both cases are right-handed and EEG abnormalities are mainly in the right hemisphere . The right hemi­sphere plays an important role in language develop­ment as well as the left.

Key words: Acquired speech disturbance, epileptic encephalopathy, ACTH-Z.

194 Brain & Development, Vol 5, No 2,1983

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The Effect of ACTH on Cerebral Function: A Neurophysiological Study Tamiko Negoro, MD, Kazuyoshi Watanabe, MD, Kazuyo Inokuma, MD, Sunao Furune, MD, Midori Sugiura, MD and Susumu Hakamada, MD Department of Pediatrics, Nagoya University School of Medicine, Nagoya, Aichi (TN, KW, KI, SF, MS); Department of Pediatric Neurology, Central Hospital, Aichi Prefectural Colony, Kasugai, Aichi (SH)

Recently , several papers have been published concern­ing CT changes after ACTH treatment. The aim of this study is to investigate the effect of ACTH on cerebral functions neurophysiologically .

Materials and Methods Six cases of secondary generalized epilepsy (SGE) and Lennox syndrome with ages between 5 and 11 were studied with power spectral analysis of occipital basic rhythms before, during, and after ACTH treatment (0.375-0 .5 mg per day ofCortrosyn-Z for 7-16 days). Auditory brainstem responses (ABR) were studied in 6 cases of West syndrome and SGE with ages ranging from 0 to 8 (0.2-0.25 mg per day of Cortrosyn-Z for patients aged 2 years or younger). Visual and auditory evoked responses (yEP, AEP) were also studied in 5 cases of West or Lennox syndromes and SGE patients with ages between 1 and 8. Power spectral analysis was performed using signal processor 7T08 and per­cent power of 6 frequency bands (DELTA: 0.1-3 .5 Hz, THETA : 3.5-7.5 Hz, ALPHAl: 7.5-10.0 Hz, ALPHA2: 10.0-13.0 Hz, BETAl: 13.0-18.0 Hz, BETA2 : 18.0-30.0 Hz) was calculated. ABR was ob­tained also using the same computer with 60dBSL click stimuli presented at 75 msec intervals through headphones. YEP was recorded using AT AC5 0 1-20 with photic stimulation of 1-2 sec intervals. AEP was also obtained using the same computer with 90dBSL click stimuli given at 2-3 sec intervals through a speaker.

Results With ACTH therapy, power spectral analysis disclosed an increased power in the slower frequency bands and the percent power of delta waves was increased and that of alpha waves was decreased even in the patients whose CT showed almost no changes. These changes were resolved after the treatment. The waveform of ABR was not so influenced with ACTH, but the latencies of waves III and V, and V-I showed a de­crease latency difference in 5 of 6 cases. The wave forms of YEP and AEP were more affected than that of ABR, and peak latencies of N 1 and P2 of YEP and P2 and N2 of AEP also showed a tendency to shorten with ACTH in some cases.

Conclusion ACTH had a profound influence on the power spec­trum of occipital basic rhythm, with increasing power in slower frequency bands, and also showed an effect on ABR, YEP, and AEP, with shortening of peak latencies in some cases.

Key words; ACTH, CT, power spectrum, ABR, VEP, AEP.

101

Anticonvulsive Effect of Ketogenic Diet in Young Mice Kazumasa Otani, MD, Yasuyuki Futagi, MD, Hiroshi Shimizu, MD, Takashi Mimaki, MD, Hyakuji Yabu­uchi, MD, Atsushi Yamatodani, MD and Hiroshi Wada, MD Department of Neuropediatrics, Osaka Medical Center for Women and Children (KO, YF, HS); Department of Pediatrics (TM, HY), Department of Pharmacology 2 (A Y, HW), Osaka University Medical School, Osaka

Anticonvulsive effect of ketogenic diet in young mice was evaluated by various experimental seizure models, and the brain levels of amino acids and catecholamines on ketogenic diet were investigated_

Materials and Methods The ddy strain mice aged 4 weeks were fed MCT milk as ketogenic diet for 14 days _ Subconvulsive dose (45 mg/kg) of pentetrazol (PTZ) was injected intra­peritoneally once a day _ Behavioral changes following administration of PTZ were classified as follows; (0) no convulsive behavior (I) minimal full seizure (2) clonic convulsion (3) tonic convulsion (4) death_

Serum 3-hydroxybutyrate was measured spectro­photometrically using the method of Williamson et al. The concentration of brain free amino acids were measured by autoanalytical high performance liquid chromatography and the concentration of brain catecholamine by high performance liquid chromato­graphical method developed by Yamatodani et al.

Results Two weeks' ketogenic diet feeding to mice showed no significant anticonvulsive effect against maximal electroshock seizure (20 mA), PTZ-induced seizure (75 mg/kg), semicarbazide-induced seizure (100 mgt kg) and hydration electroshock seizure threshold (10 mA), but significant protection against convulsion induced by daily administration of subconvulsive dose of PTZ_ In ordinary diet group (n = 10), the first seizure was developed on the third administration and 9 mice developed seizure after ten doses of PTZ_ On the other hand, in ketogenic diet group (n = 10), the first seizure was developed on the 5th administration and only three mice developed seizure even after 10 doses_

In 2 weeks' ketogenic diet feeding, serum 3-hy­droxybutyrate concentration elevated 8 to 20 fold of ordinary diet feeding_

In ketogenic diet group basic amino acids (lysine and arginine) levels remarkably decreased compared to those of ordinary diet, GABA, aspartate, glutamate and ethanolamine contents of fore brain and cysta­thionine, tyrosine and isoleucine contents of mid-hind brain slightly decreased, alanine and glutamine con­centrations of mid-hind brain slightly increased_ Noradrenaline level of fore brain in ketogenic diet group was slightly higher than in ordinary diet group, but dopamine concentration did not change_

Key words: Ketogenic diet, pentetorazol, anticon­vulsant effect, brain amino acids, brain catecholamine_

102

Treatment of Intractable Epilepsies with DN-1417 (TRH Analogue) Kenjiro Terasawa, MD, Toyojiro Matsu ish i, MD, Osamu Ishihara, MD, Kazutoyo Inanaga, MD and Seiichiro Ueda, MD Departments of Pediatrics (KT, TM, 01) and Psychia­try (KI, SU), Kurume University School of Medicine, Kurume, Fukuoka

Recent studies have shown that thyrotropin-releasing hormone (TRH) is located widely in the extrahypo­thalamic areas of the brain, and may have a function as a neurotransmitter or neuromodulator in the central nervous system (CNS) _ At the 15th annual meeting of the Japan Epilepsy Society in 1981 , Inanaga pre­sented a paper reporting the effectiveness of treating the degenerative type of myoclonus epilepsy and other intractable epilepsies with DN-1417 (a TRH analogue). DN-1417 is claimed to have a more potent and more sustained eNS action than TRH, and its TSH-releasing activity is about 1/30 that of TRH_ The present study deals with the treatment of intractable epilepsies with DN-1417 in 10 subjects consisting of 7 with Lennox syndrome, 2 with West syndrome and 1 with myo­clonus epilepsy. The dosage regimen was 30-50 IJ.g/kg/ day of DN-1417 (max. 2 mg in adults) given i.m., once a day, for 14 days in principle. The antiepileptic agents that had been prescribed before the study were all used without any modification. Evaluation of the drug efficacy was done in accordance with the criteria proposed by Inanaga et al in terms of changes in seizures (type and frequency), clinical manifestations (psychic activity and motor function) and EEG, before and 1 and 2 weeks after start of DN-1417 treatment. Evaluation was also made 4 weeks after the end of the medication if the drug efficacy was sustained. At 1 and 2 weeks of the treatment, side effects were checked as to endocrinological parameters such as TSH and prolactin, and also psychic activity and motor function. After the 2-week medication, the drug was globally evaluated for efficacy and safety. The treatment was evaluated as effective in 3 of the 7 patients with Lennox syndrome, associated with a reduction of seizures such as atypical absence, tonic seizures, tonic spasms and myoclonic seizures. Arousal EEG could be recorded in 2 patients and the basal rhythm was seen to be improved. The paroxysmal discharge disappeared in one of them and was reduced in the other. Sleep EEG was recorded in the 7 p atients and 3 showed a reduction of paroxysmal discharge. Activation of psychic activity was also noted in 4 of the 7. Further, improvement of motor function was noted in 4 of the 7. In the patient with myoclonus epilepsy, cerebellar ataxia and activities of daily life were improved. The patients with West syndrome are still under treatment with the drug, and no evaluation has been made yet . The results indicate that DN-1417 is obviously effective in some cases for treatment of intractable epilepsies, and clinical trials with the drug in a larger group of patients would be worthwhile .

Key words: TRH analog, intractable epilepsies.

Brain & Development, Vol 5, No 2, 1983 195