Shuji Miyazaki

Long‐term Prognosis after Infantile Spasms: a Statistical Study of Prognostic Factors in 200 Cases

A follow‐up study was made on 200 children (115 boys, 85 girls) who had had infantile spasms, in order to compare their present condition over the age of six years with various prognostic factors. 48 of the children (30 males and 18 females) had died, and all the rest were aged six years or older at the time of final follow‐up. 139 of the children had received ACTH therapy: at final follow‐up, spasms had ceased in 43.5 per cent, and about the same proportion showed normal physical development; 23 per cent had normal mental development and 15.4 per cent were attending ordinary schools. Complete recovery (normal mental and physical development and attending ordinary schools) was achieved in only 19 cases (9.5 per cent). Of the cryptogenic cases, 44.4 per cent had made a full recovery.

Epilepsy in Angelman syndrome associated with chromosome 15q deletion

Summary: We report eight sporadic cases of typical Angelman syndrome (AS) associated with chromosome 15q12 deletion. Age at first visit was 3–35 months (average 18 months), and follow‐up period was 4‐20 years (average 14.1 years). The characteristic features of epilepsy in AS are (a) seizure onset in early childhood (8 of 8); (b) evolution of seizure type with age (8 of 8); (c) EEG abnormality changes from high‐voltage slow bursts (HVS) in infancy to diffuse spike and waves in middle childhood (4 of 5); (d) atypical absence seizures (8 of 8), often occurring as atypical absence status (4 of 8); and (e) diminution of seizure discharges and clinical seizures after puberty (7 of 7). We believe that AS may frequently exist in the intractable epilepsies of childhood with severe mental retardation. We stress the importance of AS as one of the main etiologic background diseases of the intractable epilepsies with infantile onset such as West syndrome, Lennox‐Gastaut syndrome, and others.

Clinical Effects of Thyrotropin-Releasing Hormone for Severe Epilepsy in Childhood: A Comparative Study with ACTH Therapy

Summary: We investigated the effects and side effects of thyrotropin‐releasing hormone (TRH) on severely epileptic children to evaluate the clinical usefulness of TRH in the treatment of epilepsy and compared them with the results of ACTH therapy. The subjects were 64 patients admitted consecutively between 1980 and 1986. Their seizures were frequent, more than one a day or more than one a week. The subjects were divided into two groups; 33 patients treated with ACTH and 31 treated with TRH. The mean follow‐up periods in TRH and ACTH therapy were 8 months and 3.0 years, respectively. The daily dose of TRH‐t 0.5‐1 mg was administered intravenously (i.v.) or intramuscularly (i.m.) for 1–4 weeks. The follow‐up periods were 3–12 months (mean 6 months). In the TRH group, complete control of seizures was achieved in 7 of 13 (53.7%) of those with infantile spasms, and marked improvement of EEGs were observed in 8 of 13 (61.5%) of them. In the ACTH group, seizure cessation was observed in 75% of infantile spasms. Of the patients who received ACTH, 66.7% had various side effects, including pneumonia, huge subcutaneous abscess, hypokalemia, cataracts, and brain shrinkage as shown on computed tomography (CT), whereas only 16.7% of the patients treated with TRH had transient reduction of urine volume without other laboratory and physical abnormalities. The results of the study indicated that some patients who received TRH had cessation of infantile spasms and improved EEG findings with no serious side effect. Because of the untoward side effects of ACTH therapy, TRH is considered a possible new treatment for children with infantile spasms.

Infantile spasms: Etiological factors, clinical aspects, and long term prognosis in 200 cases

The etiological factors, clinical aspects and long term prognosis were studied in 200 patients with infantile spasms. Forty-eight (24.0%) died and the rest were aged 6 years or more at the time of final follow-up. In 73 (36.5%) the etiology was prenatal, in 44 (22.0%) perinatal, and in 17 (8.5%) postnatal: 18 cases (9.0%) were cryptogenic. The remaining 48 (24.0%) patients were doubtful cases. The mortality of the pre-and perinatal cases at 35.6% and 34.1% respectively was significantly higher than that in the other etiologic groups (P<0.001).With regard to the onset of spasms, these were very carly in the pre-and perinatal groups, whereas in the postnatal group the onset was late. The onset in the doubtful and cryptogenic groups was in between. Some 44.4% of the cryptogenic cases showed normal mental and physical development after the age of 6 years, whereas less than 10% of the prenatal and perinatal group did so. Almost all of the doubtful cases became mentally subnormal.The incidence of a family history of epilepsy or other convulsive disorders in the first, second and third degree relatives was highest in the cryptogenic cases (40.0%), and lowest in the perinatal cases (9.3%) (P<0.01). The incidence of laughing attacks was highest in the postnatal cases (42.9%), against no such attacks in cryptogenic cases (P<0.01). The attacks seemed to be linked with organic brain lesions. Among various factors related to the etiology of infantile spasms, genetic propensity seemed especially important in cryptogenic cases.

Long-term prognosis of tuberous sclerosis with epilepsy in children

A follow-up study was performed on 40 children with tuberous sclerosis and epilepsy. In 68% of the patients with infantile spasms and 73% of those without them, complex partial seizures were observed. Thus, patients with tuberous sclerosis are subject to not only infantile spasms but also complex partial seizures. Patients with infantile spasms showed mental retardation more often than those without. Seizures which had evolved from infantile spasms were more difficult to control than those which had not. The prognosis of infantile spasms associated with tuberous sclerosis was better than that of prenatal group other than tuberous sclerosis. Forty percent of the 40 cases showed asymmetry on EEG, and the asymmetry tended to disappear as the patients grew up.

The evolution of visual and auditory evoked potentials in infants with perinatal disorder

The evolutionary changes of evoked potentials (EPs) were studied from the neonatal period up to 1 year of age in 41 infants with various perinatal disorders. Abnormal EPs in the first week of life recovered quickly. In infants with normal outcome, abnormal EPs became normal within a month. In infants with cerebral palsy (CP) or mental retardation (MR), EPs recovered within 2-3 months of age. Infants with more severe neurological damage showed abnormal EPs even beyond 6 months of age. Abnormal EPs beyond 2 weeks of age indicated poor prognosis. As for the wave form of EPs, absent responses or abnormal wave form reflected more severe brain dysfunction. AEPs tended to show more profound abnormalities than VEP. However, some infants with absent AEP in the first week of life had a favorable prognosis. AEPs seemed to be more easily affected by brain dysfunction.

The evolution of electroencephalographic features in lissencephaly syndrome

The electroencephalographic features and their evolutional changes with age were described in three cases of lissencephaly syndrome diagnosed by CT scan. The case with more severe lissencephaly displayed very similar EEG findings. In early or middle infancy when infantile spasms began, EEG showed very high amplitude (more than 400 microV) slow waves mixed with sharp theta-waves. In their clinical course, they showed extreme spindles and in late infancy, the EEG revealed a tendency towards bilaterally synchronous discharges of high amplitude sharp and slow waves. On the other hand, milder forms of lissencephaly showed hypsarrhythmia in early infancy. In the late infancy the EEG showed bisynchronous sharp and slow waves of more than 200 microV. The anomaly ranging from agyria to pachygyria seems to be closely associated with varying EEG abnormalities from extremely high voltage hypsarrhythmia to focal spikes. The very high voltage of hypsarrhythmic patterns and the very low frequency of sharp wave discharges seem to be typical in the most severe lissencephaly or agyria

Neonatal seizures and subsequent epilepsy

Neonatal findings and evolutionary courses of epileptic seizures were described in newborns who had seizures during the neonatal period and later developed epilepsy. Neonates with CNS dysgenesis ran the highest risk (80%) for subsequent epilepsy. About 30% of those who suffered from perinatal hypoxia and/or intracranial birth injury and 30% of those who had meningitis developed subsequent epilepsy. In perinatal brain injury, those who developed epilepsy showed more abnormal neurological and electroencephalographic findings than those who did not. The more abnormal the neonatal background EEG, the more frequently epileptic fits developed later. There was no such relationship in CNS dysgenesis. Myoclonic seizures were associated with the most severe brain damage. Newborns who later displayed West syndrome had also very abnormal neonatal EEG whereas those who manifested other types of fits more often had less abnormal neonatal EEGs. In West syndrome, hypsarrhythmia was preceded by focal or multifocal spikes, and closely temporally related with the onset of spasms, but there was a variety of intervals between the onset of clinical fits and EEG spikes in generalized or focal motor seizures.

Development of the motor behavior during sleep in newborn infants

Body movements during sleep were examined in eight non-eventful preterm babies and two full-term babies using the polygraphic methods including superficial EMG. Typical movements in quiet sleep were startle (St) or generalized phasic movement (GPM) and increased tonic activity in chin muscles. In active sleep, instead of total simultaneous patterns observed in quiet sleep, more un-coordinated and localized movements such as generalized movement (GM), localized tonic movement (LTM), localized phasic movement (LPM) and clonic movement (CM) occurred. Longitudinal study of movements revealed a decrease of St or GPM, GM and LPM. LTM did not decrease with increasing conceptional age. The differences of decreasing tendency among these movements may indicate the differences of maturational changes in the different part of CNS.

Williams syndrome and deficiency in visuospatial recognition

This study aimed to assess the visuospatial abilities of five children with Williams syndrome (four males aged 9 years 3 months, 7 years 11 months, 8 years 1 month, and 10 years 8 months respectively, and one female aged 6 years 3 months). First, the childrens visuospatial abilities were examined by asking them to copy a figure. Second, their cognitive processing abilities were assessed using the Japanese Kaufman Assessment Battery for Children. This test was used because it is an objective one, standardized in Japan, and is a measure of fluid ability including spatial localization. Participants scored significantly low on the spatial memory subtest indicating that there was a deficit in spatial localization. Childrens performance in line copying tasks improved when the dots were in colour. Results suggest a deficit in the dorsal stream of visual cognition, with a relatively preserved ventral stream.