Tomohide Akimitsu

Effect of subthalamic stimulation on mood state in Parkinson’s disease: evaluation of previous facts and problems

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.

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.

Epileptic seizures induced by N-acetyl-l-aspartate in rats: in vivo and in vitro studies

Tremor rat (tm/tm), the parent strain of spontaneously epileptic rat (SER: zi/zi, tm/tm), exhibits absence-like seizures characterized by 5-7 Hz spike-wave-like complexes on cortical and hippocampal electroencephalograms (EEG) after 10 weeks of age, prior to development of convulsive seizures. Recently, this animal model has been demonstrated to display a genomic microdeletion within the critical region of tm, where aspartoacylase hydrolyzing N-acetyl-L aspartate (NAA) is located, besides showing the ability to accumulate NAA in the brain. Therefore, the present study was performed to determine the involvement of NAA in the induction of epileptic seizures. When NAA (4 micromol) was applied intracerebroventricularly (i.c.v.) to normal Wistar rats, 4-10 Hz polyspikes and/or spike-wave-like complexes followed by absence-like seizure before persistent 1-5 Hz waxing high-voltage after-discharges were observed on cortical and hippocampal EEG. At a higher dose (8 micromol), NAA induced convulsive seizures. The absence-like seizures with polyspikes and/or spike-wave-like complexes on the EEG were also observed with i.c.v. NAA in premature tremor rats without seizures. The NAA-induced seizures in normal rats were antagonized by i.c.v. glutamic acid diethyl ester, a non-selective glutamate receptor antagonist. In addition, NAA applied to the bath rapidly induced a long-lasting depolarization concomitantly with repetitive firings in hippocampal CA3 neurons of normal rat brain slice preparations. These findings suggest that NAA is involved in the induction of absence-like seizures and/or convulsion, probably via glutamate receptors.

Suppression by topiramate of epileptiform burst discharges in hippocampal CA3 neurons of spontaneously epileptic rat in vitro.

Topiramate, a novel antiepileptic drug, inhibits the seizures of spontaneously epileptic rat (SER), a double mutant (zi/zi, tm/tm) which exhibits both tonic convulsion and absence-like seizures from the age of 8-weeks. Hippocampal CA3 pyramidal neurons in SER show a long-lasting depolarization shift with accompanying repetitive firing when a single electrostimulation is delivered to the mossy fibers in vitro. The effects of topiramate on the excitability of CA3 pyramidal neurons in SER were examined to elucidate the mechanism underlying the antiepileptic action. Intracellular recordings were performed in 23 hippocampal slice preparations of 16 SER aged 8-17 weeks. Topiramate (10-100 microM) dose-dependently inhibited the depolarizing shifts with repetitive firing induced by mossy fiber stimulation without affecting the first spike and resting membrane potentials in hippocampal CA3 neurons of SER. Higher dose of topiramate (100 microM) sometimes inhibited the first spike, and decreased excitatory postsynaptic potentials in the SER CA3 neurons. However, topiramate up to 100 microM did not affect the single action potential elicited by the stimulation in the hippocampal CA3 neurons of age-matched Wistar rat devoid of the seizure. Application of topiramate (100 microM) did not significantly affect the firing induced by depolarizing pulse applied in the CA3 neurons of the SER. In addition, topiramate (100 microM) had no effects on the Ca2+ spike induced by intracellularly applied depolarizing pulse in the presence of tetrodotoxin and tetraethylammonium. In contrast, a dose-dependent inhibition of depolarization and repetitive firing induced by bath application of glutamate in CA3 pyramidal neurons was obtained with topiramate (10-100 microM). Furthermore, topiramate (100 microM) decreased the number of miniature postsynaptic potential of CA3 pyramidal neurons of SER. In patch clamp whole cell recording using acutely dissociated hippocampal CA3 neurons from SER aged 8-weeks and age-matched normal Wistar rats, there were no remarkable effects on voltage dependent Ca2+ current with topiramate up to 300 microM in either animal; the current was completely blocked by Cd2+ at a concentration of 1 mM. These findings suggest that topiramate inhibits release of glutamate from the nerve terminals and/or abnormal firing of the CA3 pyramidal neurons of SER by mainly blocking glutamate receptors in the neurons.

Induction of convulsive seizures by acoustic priming in a new genetically defined model of epilepsy (Noda epileptic rat: NER)

Noda epileptic rat (NER) is a mutant rat, found in a Crj: Wistar colony, which exhibits a tonic clonic convulsion spontaneously about once per 30 h from 14 weeks of age. We performed modified acoustic priming, that is, repeated weekly sound stimulations from 3 weeks of age. In addition, characteristics of audiogenic seizure (AGS), and ictal/interictal electroencephalograms (EEGs) were examined. We also studied the effect of repeated weekly stimulations from 14 weeks of age on AGS susceptibility in another NER. From 9 weeks of age, the NER primed from 3 weeks of age had a high incidence (100%) of AGS: a typical seizure was composed of sudden wild running and/or jumping (WRJ) followed by clonic or tonic-clonic convulsion. The severity and the duration of the AGS were intensified and prolonged with an increase in age, respectively. By contrast, the NER repeatedly stimulated from the age of 14 weeks, rarely showed AGS (20-40(%). The majority of the seizures in this NER were WRJ. The cortical and hippocampal EEG during the tonic convulsion showed a low-voltage spike-wave (5-7 Hz). This evolved into a high-amplitude spike- or polyspike-waves associated with the clonic convulsion. Immediately after cessation of the seizures, the EEG showed a flattening or diffuse slowing. In interictal EEG analysis, sporadic spikes predominantly in the hippocampus and spike-wave bursts in both the cortex and hippocampus occurred from 11 and 20 weeks of age, respectively. These results indicate that AGS susceptibility in NER can be induced consistently by modified acoustic priming and this rat strain is a new genetic model useful for experimental studies of human epilepsy.

Infundibuloneurohypophysitis presenting a large sellar-juxtasellar mass: case report.

BACKGROUND Infundibuloneurohypophysitis (INH) is reported to be a self-limiting inflammatory disease involving neurohypophysis. The authors experienced a case of INH presenting a large mass compressing the brain stem. CASE PRESENTATION The patient exhibited polyuria followed by left hemiparesis and dysarthria lasting a year. Magnetic resonance imaging showed a large sellar mass extending into the right cavernous sinus and prepontine cistern and compressing pons. Endocrinologically, diabetes insipidus was diagnosed and anterior pituitary function was almost normal. Microscopic examination of the surgical specimen obtained by a transsphenoidal route demonstrated diffuse infiltration of lymphoid cells with predominance of B cells over T cells and the granulation tissue. The patient underwent 40 Gy local radiation because of initial misinterpretation of histologic findings as malignant lymphoma and short-term corticostertoid administration. CONCLUSION The mass gradually shrank and the patient has become neurologically intact in 6 months. At this moment, 67 months after the onset, the patient is free from disease and has no other lesion. INH seems to be a clinical entity possessing a wide spectrum from infundibular tumorlet to an aggressive sellar mass trespassing on surrounding structures.

Abnormality of Ca2+ Channels in CA3 Pyramidal Neurons of Noda Epileptic Rats (NERs)

Purpose: The Noda epileptic rat (NER), which was found in a colony of Crj‐Wistar rats, shows spontaneous tonic‐clonic convulsions. After 8–16 weeks of age, a long‐lasting depolarization shift accompanied by repetitive firing is observed in the CA3 pyramidal neurons of the hippocampus in NERs with seizures. This electrophysiologic study using hippocampal slice preparations from NERs was performed to determine whether this abnormal firing in CA3 neurons developed with age. and its probable relationship with the abnormality of Ca2+ channels was investigated pharmacologically.

Novel Software for Performing Leksell Stereotactic Surgery without the Use of Printing Films: Technical Note.

Hospitals in Japan have recently begun to employ the DICOM viewer system on desktop or laptop monitors. However, conventional embedding surgery for deep-brain stimulation with the Leksell stereotactic system (LSS) requires printed X-ray films for defining the coordination, coregistration of actual surgical films with the reference coordinates, and validation of the needle trajectories. While just performing these procedures on desktop or laptop monitors, the authors were able to develop novel software to facilitate complete digital manipulation with the Leksell frame without printing films. In this study, we validated the practical use of LSS, and benefit of this software in the Takanobashi Central Hospital and Kagoshima University Hospital.

Abnormal Excitability of Hippocampal CA3 Neurons in Noda Epileptic Rat (NER): Alteration of Seizure with Aging

Purpose: Noda epileptic rat (NER), a mutant found in thc colony of Crj:Wistar rats, spontaneously shows tonic‐clonic convulsions approximately once every 30 hours from 8–16 weeks of age. A long‐lasting dcpolarization shift accompanied by repetitivc firings are observed in hippocampal CA3 pyramidal neurons of NER with seizures. Using hippocampal slice preparations of NER, the present electrophysiologi‐ cal study was performed to elucidate whether this abnormal firing in CA3 neurons developed with age and if abnormality of Ca2+ channel was involved.

Age-dependent abnormal excitability of hippocampal CA3 neurons of noda epileptic rats (NER)

The Mongolian gerbil (Meriones unguiculatus) is a genetic animal model of epilepsy. In a seizure-sensitive strain that we have established, posture change, a potent seizure-inducer in adults, induces rhythmical backward movement of the pinnae in young animals. A major stimulus during posture change is vestibular; the vestibular cortex was localized in the somatosensory area and electrical stimulation of this site induced backward movement of the pinnae. Since this site may be involved in seizure, we studied its electrophysiological characteristics, using a telemetry machine. A puff of air was found to induce a sharp EEG wave in the region that includes the vestibular cortex; this effect and the movement of the pinnae were often repeated on stimulus cessation. Animals that had not undergone surgery also showed repetitive ear movement under similar conditions, suggesting that these electrophysiological features do no result from surgery, but are intrinsic to this strain.