A molecular-genetic study was performed in 61 patients with Angelman syndrome (AS) and 14 patients with Prader-Willi syndrome (PWS). Southern blot analyses and/or PCR-mediated dinucleotide repeat polymorphism (DNRP) analyses revealed that 67% of AS patients have DNA deletions ranging from D15S9 to D15S12 loci. An exception was 3 sib cases whose deletion involved only 2 loci, D15S10 and GABRB3. The parental origin of the deletions in AS patients were exclusively maternal. No uniparental disomy (UPD) was found in our AS patient series, suggesting that UPD in AS is infrequent than that in PWS. Molecular deletions were observed in 6 of the 14 PWS patients.
In order to develop a simple, reliable DNA-based diagnostic method, I adopted PCR-mediated DNRPs as genetic markers for the detection of deletions and/or parental origin of chromosomes 15 in AS and/or PWS patients. This method gave useful diagnostic information in 33 (89%) of 37 AS patients and 12 (86%) of 14 PWS patients, indicating no big difference from the information obtained with Southern blot analysis. Furthermore, since this DNRP method dose not require radioisotopes, it may be a first-choice, alternative way when diagnosing AS or PWS patients.

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To estimate the primary focus in 17 epileptic children with multifocal spikes, simultaneous averaging of spikes in 16 channels was performed. At first, EEG was recorded on EEG-video monitoring tape. Then, the computer sampled the data every 5 msec through an A-D converter, and stored the corresponding digital values. We used the top of the spike as a trigger point, and averaged 7 to 50 spikes in each lead. The primary focus and areas propagated from it were determined from the latency between the averaged spikes in different leads. We defined multiple foci when morphologically different averaged spikes were independently present in different leads.
The averaging method could narrow the areas with spike discharges in 16 of 17 patients, and define a single focus in 6 patients. Furthermore, the single or unilateral foci in averaged data were compatible with the site estimated from lateralizing signs, such as lateral version of head and eyes in 3 of 8 patients. The other 5 patients showed independent bilateral foci, one of whom received focal resection of right anterior frontal lobe which was responsible for ictal symptoms and seizure discharges. Since then, seizures and right frontal epileptic discharges have not been observed but the spikes in left anterior frontal lobe have been left. These findings suggest that averaging of epileptic discharges is useful for determination of primary focus and for differentiation of true multiple foci from secondary propagation.

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Auditory event-related potentials (ERPs) were recorded in 35 epileptic children of 9 to 13 years of age, and compared with conventional test batteries of cognitive functions. ERPs were elicited with the auditory oddball paradigm.
Corrected P300 latencies showed an inverse correlation with the total score (IQ) of WISC-R and that of the Wechsler memory scale (WMS). A strong inverse correlation was also observed with specific items of these test batteries, as follows; “comprehension”, “picture completion” and “coding” in WISC-R, and “associated learning”, “digit span”, “visual reproduction”, “mental control”, “orientation” and “information” in WMS.
These findings suggested that the prolongation of P300 latencies in epileptic children are related with the impairment of cognitive functions. The P300 latency is correlated with a characteristic kind of cognitive function ; “simple recognition”, “short term memory” and “easy judgement”.

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We studied the prognosis of twenty-five idiopathic status convulsivus (SC) patients. They were neurologically normal before the onset, and had the first episode of idiopathic SC, defined as a seizure with a duration of longer than 30 minutes, febrile in 18 cases and afebrile in 7 cases. We excluded acute encephalitis, encephalopathy and past history of epilepsy in all patients.
The age of the first SC ranged from 3 months to five years and 3 months (median; 1 year and 9 months). They were followed successively for a period of 3 years to 15 years and two months (median 8 years and 7 months). The final diagnosis was epilepsy in 7 cases, epilepsy border in 11 cases, and febrile convulsion in 7 cases.
One patient showed a remarkable learning disability, but no patients had psychomotor retardation.
Antiepileptic drugs were given 24 patients, all of whom were well controlled, including 17 cases with successful withdrawal of these drugs. In our febrile convulsion cases, there was no more than one risk factor for the development of epilepsy (Awaya). The prognosis of febrile SC cases was favarable.

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We studied the etiology for sixty-eight severely handicapped children aged between 3 and 6 years, who were born in the Himeji city and the environs (9, 900 live births/year). The prevalence was around 1.7/1, 000 live births. The factors of their handicaps were as follows: congenital 25%; perinatal 40%; neonatal period 21%; and unknown onset 15%. Thirty-six patients out of 54 (67%) were admitted to neonatal intensive care unit (NICU) and visited the Center for neurological follow up immediately after their discharge. The high frequency of patients from NICU, compared with previous reports, might be due to a cooperative network between NICUs and the Center with medical support for handicapped children in this area.

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We studied the etiology of 76 children with cerebral palsy (CF) aged 3 to 6 years, who visited the Himeji City Center for the Handicapped for neurological follow up. The patients for this study composed of 30 cases with severe handicap. 8 cases of CP with mental retardation and 10 cases of CP without mental retardation. Nine cases of CP had congenital anormalies of central nervous system, of which 8 cases showed severe handicap. Main perinatal factors were asphyxia, dyspneic condition needed for mechanical ventilation, prolonged apneic spells, and hyperbilirubinemia. All full-term birth children were accompanied with asphyxia, in which 43% had intracranial hemorrhage. A cooperative network between neonatal intensive care unit and an institute for the handicapped is essential for the care of infants with cerebral palsy.

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Neuroradiological and neurophysiological studies were done in two male siblings with carbohydrate-deficient glycoprotein syndrome (CDGS) (case 1 and 2) and one male second cousin presumed with CDGS (case 3). Case 1 and 2 had abnormality of epileptic discharge in EEG. Case 1 had MCV in the lowest normal range, giant SEP was observed in SSEP in case 1 and low voltage of P 14 in case 3. Case 1 had low voltage of wave V in ABR and case 3 had low voltage of wave V on one side and no response on the other side. The all cases showed the normal pattern for VEP and MEP. All showed cerebellar hypoplasia and various degree of pontine hypoplasia on MRI. SPECT showed hypoperfusion in cerebellum, brainstem and left centroparietal region in case 1. In CDGS we found the hypoplasia of cerebellum and pons in common, but it was suggested that CDGS might have the heterogeneity of pathophysiology on the basis of various neurological abnormalities.

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The author investigated medical circumstances of the severely mentally and physically handicapped children who needed to be treated for more than one month at general hospitals in Sapporo district using a questionaire method followed by a direct observation. Fifty patients were identified and their chronological ages distributed from 5 months to 19 years old. The mean period of hospitalization was approximately 2 years. They could be roughly devided into two groups; high risk infants for severely mental and physical handicap; and the most severely mentally and physically handicapped teens needing hospital treatment for their lives. Etiology was congenital in 38%(CNS malformations, neuromuscular diseases, etc.), acquired in 36%(hypoxic brain damage due to accidents, CNS infections, etc.) and perinatal in 26%(all hypoxic ischemic encephalopathies). More than 90% of the patients showed abnormal brain CT scan and 20% had visual and/or auditory disturbances. A half of them needed artificial ventilation supports and/or tracheal canulation. More than 60% received tube feeding therapies. From this evidence, it is considered that the long term hospitalized severely mentally and physically handicapped children have severe brain dysfunction which needs high medical technology and professionals. It seems that a little remedial supports to them is done in general hospitals at present in Sapporo district. Comprehensive treatment will hopefully be done for them in the near future.

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Benign childhood epilepsy with centrotemporal spike (s) (BCECT) is characterized by rolandic discharges (RD) on EEG. As the origin of RD, the lower rolandic cortex was proposed by Lombroso, but recently the hippocampus was proposed by some reports, based on the character of RD or the pharmacological effects of anticonvulsants. On the other hand, MRI hippocampal volumetric measurements revealed the relationship between the hippocampal atrophy and EEG foci in intractable temporal lobe epilepsy (TLE) of adults, but there are a few reports of the hippocampal volumetric study in children. Therefore, in this paper, we reported about MRI hippocampal volumetric measurements in BCECT and TLE of childhood onset. The statistical examination was performed by t-test.
MRI hippocampal volumetric measurements were performed in 27 cases with BCECT (6-19 years, 9.9 2.7 years, 11 males, 16 females), 22 cases with TLE (5-22 years, 12.9± 5.5 years, 15 males, 7 females) and 17 normal control subjects (6 15 years, 10.4 ± 2.7 years, 10 males, 7 females). The age was not significantly different among the 3 groups. The clinical course of TLE group was significantly longer than BCECT group, but the onset age of epilepsy was not significantly different between the 2 groups. The hippocampal volume and the right-side minus left-side volume were not significantly different in 3 groups, but these values of TLE were more scattered than the others. There was no abnormal signal intensity in hippocampus on MRI, or no specific abnormality in the surrounding structures in 3 groups. Consequently, no organic lesion was found in BCECT on brain MRI. The investigation about the hippocampal atrophy in TLE suggested that the history of febrile convulsions and the length of clinical course were related to the hippocampal atrophy.

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We report a patient with methylmalonic acidemia who developed an acute extrapyramidal disorder after severe ketoacidosis. The neurologic findings resulted from bilateral destruction of the globus pallidus.
A 10-year-old girl was the term product of an uncomplicated pregnancy and delivery. Poor feeding and vomiting were noted after one month. She was hospitalized at 6 months of age with vomiting, coma and tachypnea. Analysis of urinary organic acids revealed a massive amount methylmalonic acid. She was not vitamin B 12-responsive and was maintained on a low-protein diet. At 33 months of age, she was able to walk and speak, but she developed acute severe ketoacidosis. Involuntary movements and spastic paraplegia became evident two days after admission. Subsequently, the patient has had metabolic ketoacidosis once or twice a year. Her intelligence quotient was 47. Neurologic examination revealed spastic paraplegia and generalized hypotonicity with mild dystonia. Some relief from dystonic symptoms has been obtained through the use of L-dopa.
A brain CT scan at 5 years of age disclosed bilaterally symmetric lucencies of the globus pallidus. T2-weighted brain MRI at 8 years of age showed bilateral symmetric high intensities of the globus pallidus.

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A 10-year-old boy with palmoplantar hyperkeratosis and keratitis was reported. His physical development was normal and mental development was lower limit. He had also convulsions with low grade fever several times, and his EEG showed paroxysmal discharges. The plasma levels of phenylalanine and tyrosine were 5 to 10 times higher than those of controls. Tyrosinemia II was diagnosed on the low level of cytosol tyrosine aminotransferase in biopsied liver. The cases of tyrosinemia II were reviewed on the symptoms of the central nervous system. Two of twelve cases had convulsions. Adult cases demonstrated nystagmus, tremor, ataxia, and convulsion. Hyperkeratosis and corneal lesions were characteristic in symptoms of tyrosinemia II, but attention should be paid to the symptoms of the central nervous system.

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A healthy boy who had showed no evidence of cerebral lesions developed epileptic seizures resembling grand mal during nocturnal sleep at the age of 9 years and 2 months. Interictal EEG showed diffuse sharp waves that were maximal in the right centroparietal area and recurred at short intervals. Polysomnography for one night was performed when the patient was 9 years and 11 months old. The values of sleep variables (percentage of sleep period time for each sleep stage, sleep latency, REM density) were within normal limits. Interictal sharp waves appeared most frequently in the stages 3 and 4, and least in the stages REM and W. Partial seizure of the left face occurred with impaired consciousness in the stage 2 at around 5 a. m. On the ictal EEG, a low-voltage fast discharge was initiated in the right frontal area, followed by a diffuse rhythmic discharge of high voltage at 5-6 Hz, which was associated with a clinical seizure. The seizures completely ceased within one month after the polysomnography. Interictal sharp waves that migrated to the centrotemporal or midtemporal area disappeared at the age of 15 years and 9 months. The patient is now 19 years and 5 months of age. Although his interictal EEG and clinical seizures were atypical, we diagnose his disease as benign childhood epilepsy with centrotemporal spike based on the the polysomnographic findings and the clinical and EEG follow-up.

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[in Japanese]

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[in Japanese]

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