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. Key Words: Tremor rats-Epilepsy-Neurodegeneration-Positional cloning-Aspartoacylase -N-Acetyl-L-aspartate. J. Neurochem. 74, 2512Neurochem. 74, -2519Neurochem. 74, (2000.Epilepsy is a diverse neurological abnormality that is characterized by recurrent seizures, affecting 1-2% of the population worldwide (McNamara, 1999). Epileptic seizures comprise alterations in sensory and motor systems and in consciousness. They result from the disordered, synchronous, and rhythmic firing of certain populations of neurons in the CNS. Current therapies are not satisfactory, as they do not provide symptomatic relief in some subsets of affected individuals and are sometimes accompanied by toxic effects. Elucidation of the cellular and molecular mechanisms underlying epileptogenesis, therefore, should lead to the development of new fundamental therapies and prevention methods, or even a cure. Seizure disorders or epilepsy syndromes are presently classified into Ͼ40 distinct types (Commission on Classification and Terminology of the International League Against Epilepsy, 1989). Although most epilepsies are considered to be multifactorial diseases, some specific types are considered single-gene disorders (Steinlein et al., 1995;Pennacchio et al., 1996;Biervert et al., 1998;Charlier et al., 1998;Fox et al., 1998;Singh et al., 1998;Wallace et al., 1998;McNamara, 1999).The tremor rat is a single-gene mutant found in the Kyoto:Wistar colony that exhibits absence-like seizure characterized by sudden immobility and staring, simultaneously with the appearance of 5-to 7-Hz spike-wave complexes in cortical and hippocampal EEG (Yamada et al., 1985;Serikawa et al., 1987;Hanaya et al., 1995). Homozygous rats (tm/tm) for the causative genetic locus tremor (tm) exhibit absence-like seizure after the age of 14 weeks, whereas heterozygotes (tm/ϩ) exhibit the same seizure less frequently after 26 weeks (Higashiguchi et al., 1991). In older age groups, wild running and jumping episodes are sometimes observed in tm/tm rats. However, spongiform degene...

We describe two previously healthy children who had multiple ecchymoses several days after acute infection. In both cases, the prothrombin time (PT) and the activated partial thromboplastin time (APTT) were prolonged. Further examinations revealed the presence of lupus anticoagulant (LA), phosphatidylserine-dependent antiprothrombin antibodies (aPS/PT), and low serum complement. In both cases, we confirmed the presence of a serum immune complex. The patients' symptoms improved spontaneously within 1 week, and all laboratory data normalized within several months. We also describe another asymptomatic case positive for LA and aPS/PT presumably associated with cytomegalovirus infection. The prevalence of transient antiphospholipid antibodies associated with viral infections in children must be much higher than we expected. We have to take it into consideration when we see abnormal coagulation results, but the occurrence of significant bleeding symptoms is rare.

Summary:Purpose: To report on sibling cases with benign familial neonatal convulsions (BFNC) followed by benign epilepsy with centrotemporal spikes (BECT).Methods: Case histories and EEGs were obtained for the two siblings with neonatal and subsequent epileptic seizures in one pedigree with BFNC.Results: The family included six affected cases of BFNC in two generations: the proband, the proband's mother and two sisters, and the proband's maternal uncle and his daughter. The proband developed a generalized tonic convulsion 2 days after birth with no apparent cause and normal interictal EEG, and experienced a total of 18 episodes of tonic or clonic seizures or both by age 9 months. In the follow-up course, an EEG recording showed rolandic discharges at 2 years, and a sylvian seizure occurred at 4 years during sleep. On carbamazepine therapy, the last seizure was recorded at 9 years after a total of 1 1 episodes of sylvian seizures, with normal EEGs after 12 years. The proband's sister experienced nine episodes of brief tonic seizures between 7 and 9 days after birth, and also developed eight episodes of sylvian seizures from 4 to 7 years, with rolandic discharges on EEG until age 9 years. All of the family members had normal psychomotor development, with no neurologic sequelae.Conclusions: This report of BFNC followed by BECT in sibling cases is significant in view of the genetic analysis and the classification of epilepsies and epileptic syndromes.

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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.