Toshiro Maihara

Accumulation of N-Acetyl-L-Aspartate in the Brain of the Tremor Rat, a Mutant Exhibiting Absence-Like Seizure and Spongiform Degeneration in the Central Nervous System

Abstract: The tremor rat is a mutant that exhibits absence‐like seizure and spongiform degeneration in the CNS. By positional cloning, a genomic deletion was found within the critical region in which the aspartoacylase gene is located. Accordingly, no aspartoacylase expression was detected in any of the tissues examined, and abnormal accumulation of N‐acetyl‐L‐aspartate (NAA) was shown in the mutant brain, in correlation with the severity of the vacuole formation. Therefore, the tremor rat may be regarded as a suitable animal model of human Canavan disease, characterized by spongy leukodystrophy that is caused by aspartoacylase deficiency. Interestingly, direct injection of NAA into normal rat cerebroventricle induced 4‐ to 10‐Hz polyspikes or spikewave‐like complexes in cortical and hippocampal EEG, concomitantly with behavior characterized by sudden immobility and staring. These results suggested that accumulated NAA in the CNS would induce neuroexcitation and neurodegeneration directly or indirectly.

Correlation between genetic and cytogenetic maps of the rat

To correlate rat genetic linkage maps with cytogenetic maps, we localized 25 new cosmid-derived simple sequence length polymorphism (SSLP) markers and 14 existing genetic markers on cytogenetic bands of chromosomes, using fluorescence in situ hybridization (FISH). Next, a total of 58 anchor loci, consisting of the 39 new and 19 previously reported ones, were integrated into the genetic linkage maps. Since most of the new anchor loci were developed to be localized near the terminals of the genetic or cytogenetic maps for each chromosome, the orientation and coverage of the whole genetic linkage maps were determined or confirmed with respect to the cytogenetic maps. Thus, we provide here a new base for rat genetic maps.

Benign Familial Neonatal Convulsions Followed by Benign Epilepsy with Centrotemporal Spikes in Two Siblings

Summary: Purpose: To report on sibling cases with benign familial neonatal convulsions (BFNC) followed by benign epilepsy with centrotemporal spikes (BECT).

NER rat strain: a new type of genetic model in epilepsy research.

Summary: Purpose: We characterized and evaluated as an animal model of epilepsy NER, a new epileptic rat strain, which was developed by inbreeding rats with spontaneous tonic‐clonic seizures in a stock of Crj:Wistar.

Chromosomal mapping of genes for epilepsy in NER : a rat strain with tonic-clonic seizures

Summary: Purpose: NER is a mutant rat strain that exhibits spontaneous tonic‐clonic convulsions accompanied by epileptic discharges on ictal EEG and serves as a model for generalized tonic‐clonic seizures in humans. Our previous experiments have suggested that a major autosomal recessive gene and several minor genes regulate the inheritance of tonic‐clonic seizures in NER. The purpose of this study was to confirm the mode of inheritance and to locate the causative genes for epilepsy in NER on the rat genetic map.

Leigh syndrome associated with West syndrome

Leigh syndrome (LS) (sub-acute necrotizing encephalomyelopathy) is characterized by symmetric brain lesions occurring mainly in the basal ganglia and associated with variable clinical manifestations such as hypotonia, psychomotor retardation, and feeding difficulties. Patients with LS may develop seizures. Only three patients with LS have been identified in the literature as having West syndrome (WS). We have seen 12 children with LS in the past 20 years, and noticed that as many as five of them developed WS. This report discusses five LS children with WS, comparing them with seven LS children without WS. In all five patients, infantile spasms developed after LS had become evident, in addition to other type(s) of seizures. The onset of LS in all the patients with WS was before 10 months of age. Although not statistically proven, early onset of LS, spasticity, nystagmus, apnea, poor feeding, and cardiac problems seemed to be associated with the development of WS. We were not able to conclude that certain types of symptoms or examination results of patients with LS indicated the development of WS. The association of LS with WS did not markedly influence the prognoses of the children. WS may not be a rare complication of LS, especially in infants under 12 months of age. This report is the first review of LS associated with WS.

Mapping of 20 polymorphic DNA markers in the rat by somatic hybrid and linkage analysis

1Institute of Laboratory Animals, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-01, Japan 2Department of Pediatrics, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-01, Japan 3Laboratory Animal Science and Toxicology Laboratories, Sankyo Co., Ltd., Shizuoka 437, Japan 4Department of Geriatric Medicine, Osaka University Medical School, Osaka 565, Japan 5Wellcome Trust Centre for Human Genetics, Nuffield Orthopedic Centre, University of Oxford, Windmill Road, Oxford OX3 7BN, U K

Epilepsy in children with trisomy 18.

Although the reported incidence of epilepsy associated with trisomy 18 is 25–50%, there have been no detailed descriptions of the characteristics of trisomy 18‐related epilepsy. We investigated the characteristics of epilepsy in children with trisomy 18 who remained alive for over 1 year by sending questionnaires to pediatric neurologists belonging to the Kyoto Multi‐institutional Study Group of Pediatric Neurology. Eleven patients with trisomy 18 were enrolled (age at the study, from 15 to 134 months; median, 43 months), of whom seven (64%) had epilepsy. The age at seizure onset ranged from 1 to 42 months (median: 11 months). Among the seven patients with epilepsy, two had focal epilepsy, four had generalized epilepsy including infantile spasms in three, and the remaining one had an unclassified type. Seizure seminology included complex partial seizures in both the patients with focal epilepsy. At the time of the investigation, three children with generalized epilepsy still had daily seizures, while the remaining four were seizure‐free. In conclusion, the characteristics of epilepsy in patients with trisomy 18 were as follows: over half of the children developed epilepsy during infancy or early childhood; infantile spasms might be one of the common epileptic syndromes; the epilepsy was intractable in half of the children, especially in those with generalized epilepsy.

[18F]-Fluorodeoxyglucose-positron emission tomography findings in preterm infants with severe periventricular leukomalacia and hypsarrhythmia

Abstract Two preterm infants with extensive periventricular leukomalacia (PVL) were examined by [18F]-fluorodeoxyglucose-positron emission tomography (FDG-PET) at the corrected ages of 18 and 34 days. They showed similar clinical courses including oculoclonic seizure, hypsarrhythmia and severe mental retardation, in addition to spastic quadriplegia. FDG-PET study of these two infants with severe PVL disclosed poorly developed metabolic activity in the primary sensorimotor cortex, while the MRI images displayed only periventricular white matter lesions. Conclusion Positron emission tomography may dis‐close cortical involvement in infants with severe periventricular leukomalacia.

Congenital bilateral perisylvian syndrome: First report in a Japanese patient

SummaryA Japanese boy with congenital bilateral perisylvian syndrome is described. He had oropharyngoglossal dysfunction and severe dysarthria. Magnetic resonance imaging of the brain, disclosed bilateral perisylvian malformations suggesting polymicrogyria. The patient also showed mental retardation, epilepsy, and poor motor skills.