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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...

The authors report on a patient who exhibited intractable epilepsy due to an inaccessible hypothalamic hamartoma and subsequently underwent stereotactic radiosurgery. This 25-year-old man had a 24-year history of intractable gelastic and tonic-clonic seizures. Magnetic resonance (MR) imaging performed at examination as well as that performed 30 months earlier demonstrated a nonenhancing and nonprogressive spherical mass, approximately 10 mm in diameter, located on the patient's right side at the floor of the third ventricle. Focal radiation treatment performed with a gamma knife unit administered 36 Gy to the center and 18 Gy to the periphery of the lesion. This treatment resulted in an improvement in seizure control. Before the patient underwent radiosurgery, he suffered from three to six generalized seizures per month in spite of attentive compliance with an anticonvulsant medication regimen. After irradiation of the harmatoma, the frequency of the seizures transiently increased and then subsided 3 months posttreatment. The patient has been free of seizures for the last 21 months, with no neurological or endocrinological complications. Magnetic resonance imaging performed 12 months posttreatment demonstrated complete disappearance of the lesion.

In an attempt to clarify the effect of deep brain stimulation (DBS) to the subthalamic nucleus (STN) on mood state, previous evidence and problems were evaluated through a systematic literature search. Twenty three articles reported the effect of STN DBS on mood state in Parkinson's disease (PD), and antidepressant, depressant, and mania-induced effects were reported in 16.7-76%, 2-33.3%, and 4.2-8.1% of the patients treated with STN DBS, respectively. Most articles reported larger subgroups showing antidepressant effects than those showing depressant effects. The average depression scale score of all subjects was improved or unchanged after STN DBS. Although there was a limitation due to the varied results, it was suggested that, in general, STN DBS had an antidepressant effect in PD. However, the studies reporting severe depressant symptoms, such as suicidal attempts, after STN DBS indicated the importance of careful attention to mood state as well as to motor symptoms after STN DBS. It may be crucial to reduce the variation in the results by, for example, the use of standardized protocols and the precise verification of the stimulated region in further investigations to address this issue.

The signals of lactate and lipids partially overlap in single-voxel proton MR spectroscopy (1HMRS), sometimes making them difficult to differentiate in clinical settings. Our aim in this study was to identify lactate and lipids by varying the echo time (TE). We expect that the accurate detection of lactate and lipids will have high diagnostic value in the diagnosis of brain tumors. Following our protocol, we obtained meaningful 1HMRS spectra from 213 patients, including 163 patients with brain tumors, between August 1999 and February 2004. 1HMRS was performed with a TE of 144 ms followed by a TE of 30 ms and/or a TE of 288 ms, if necessary. For the 213 patients, lactate level was "negative" in 47 patients, "positive" in 131 patients, and "strongly positive" in 35 patients. The lipid level was "negative" in 90 patients, "positive" in 56 patients, and "strongly positive" in 67 patients. Based on logistic discriminant analyses of neuro-epithelial tumor WHO grade and lactate and lipid levels, lactate and lipid levels were significant between WHO grades 2 and 3 (P=0.0239) and between grades 3 and 4 (P=0.0347). Lipids are a more significant factor for the discrimination between WHO grades 2 and 3 (P=0.0073) and between grades 3 and 4 (P=0.0048). With our method of varying the TE, it is possible accurately and efficiently to detect lactate and lipids in the brain. We found a significant correlation between lactate and lipid expression and WHO grade of neuro-epithelial tumors.