Entry point to the Sylvian fissure for the pterional transsylvian approach.

BACKGROUND: Although the anatomy of the Sylvian fissure is understood, there is little information on where to start its dissection in the pterional transsylvian (PT-TS) approach. At small craniotomy using the PT-TS approach, we set the entry point to the Sylvian fissure at 15 mm behind the anterior edge of the craniotomy along the Sylvian fissure and designated this site "point 15." Here we compared the utility of "point 15" with the Sylvian point (point on the Sylvian fissure giving rise to the horizontal and anterior ascending rami) that had been recommended earlier as the entry site for opening the Sylvian fissure. MATERIALS AND METHODS: This study includes 16 patients with 7 ruptured and 9 unruptured anterior circulation aneurysms. We evaluated the usefulness of "point 15" in the PT-TS approach for aneurysmal neck clipping with respect to the adequacy of anatomical exposure and low invasiveness. RESULTS: In 12 patients "point 15" provided for excellent anatomical exposure of the Sylvian fissure; complete neck clipping was possible with minimal brain retraction and damage. In two patients with ruptured aneurysms and thick subarachnoid hemorrhage and in two patients with unruptured aneurysms, the dissection had to be enlarged 3 to 4 mm distally without reaching the Sylvian point. In the latter two patients the Sylvian veins were tethered to frontal and temporal lobes. CONCLUSIONS: The "point 15" was an easily set entry point to the Sylvian fissure. It provided for sufficient anatomical exposure at surgery for anterior circulation aneurysms; additional posterior dissection was required in rare cases. We found that "point 15" was useful in small craniotomies using the PT-TS approach.

Low distribution of synaptic vesicle protein 2A and synaptotagimin-1 in the cerebral cortex and hippocampus of spontaneously epileptic rats exhibiting both tonic convulsion and absence seizure.

The spontaneously epileptic rat (SER) is a double mutant (zi/zi, tm/tm) which begins to exhibit tonic convulsions and absence seizures after 6 weeks of age, and repetitive tonic seizures over time induce sclerosis-like changes in SER hippocampus with high brain-derived neurotrophic factor (BDNF) expression. Levetiracetam, which binds to synaptic vesicle protein 2A (SV2A), inhibited both tonic convulsions and absence seizures in SERs. We studied SER brains histologically and immunohistochemically after verification by electroencephalography (EEG), as SERs exhibit seizure-related alterations in the cerebral cortex and hippocampus. SERs did not show interictal abnormal spikes and slow waves typical of focal epilepsy or symptomatic generalized epilepsy. The difference in neuronal density of the cerebral cortex was insignificant between SER and Wistar rats, and apoptotic neurons did not appear in SERs. BDNF distributions portrayed higher values in the entorhinal and piriform cortices which would relate with hippocampal sclerosis-like changes. Similar synaptophysin expression in the cerebral cortex and hippocampus was found in both animals. Low and diffuse SV2A distribution portrayed in the cerebral cortex and hippocampus of SERs was significantly less than that of all cerebral lobes and inner molecular layer (IML) of the dentate gyrus (DG) of Wistar rats. The extent of low SV2A expression/distribution in SERs was particularly remarkable in the frontal (51% of control) and entorhinal cortices (47%). Lower synaptotagmin-1 expression (vs Wistar rats) was located in the frontal (31%), piriform (13%) and entorhinal (39%) cortices, and IML of the DG (38%) in SER. Focal low distribution of synaptotagmin-1 accompanying low SV2A expression may contribute to epileptogenesis and seizure propagation in SER.

Microvascular decompression for trigeminal neuralgia due to compression by the vertebral artery: report of 3 cases.

BACKGROUND: Trigeminal neuralgia elicited by the vertebral artery is unusual. According to a large trigeminal neuralgia series, only 4 of 1,404 (0.3%) consecutive patients with typical trigeminal neuralgia presented with vertebral artery compression. In such cases the vertebrobasilar system tends to be atherosclerotic, ectatic, and tortuous, requiring, in addition to an ordinary microvascular decompression method, technical modifications of this procedure. We report on 3 patients with trigeminal neuralgia due to compression by a tortuous vertebral artery. PATIENTS: All 3 patients underwent microvascular decompression via a small lateral suboccipital craniotomy. Operative exposure demonstrated that the root of the trigeminal nerve was compressed directly and stretched by a loop of the vertebral artery. The compression was successfully released by dislocation of the loop using Teflon (polytetrafluoroethene) slings. Immediately after the operation all 3 patients became pain-free. CONCLUSION: Among the surgical procedures used in microvascular decompression surgery, dislocation of the offending vessel with Teflon slings is a useful surgical technique to treat trigeminal neuralgia due to a tortuous vertebral artery.

N-acetyl-L-aspartate activates hippocampal CA3 neurons in rodent slice preparations.

High N-acetyl-L-aspartate (NAA) levels prevail as a free amino acid in vertebrate brains. NAA is synthesized from aspartate and acetyl Co-A, or is liberated by the hydrolyzation of N-acetyl-L-aspartyl-glutamate in mitochondria before being metabolized by aspartoacylase to aspartate and acetate in the cytosol of glial cells. The tremor rat (tm/tm), derived from a Kyoto-Wistar colony, shows absence-like seizures with 5- to 7-Hz spike-wave-like complexes in cortical and hippocampal electroencephalograms (EEG). Genomic microdeletion was found within the aspartoacylase-encoding tm critical region, where an increase in the NAA level was noted. Intracerebroventricular NAA induced absence-like seizures, convulsive seizures or both in epileptic EEG of Wistar rats. NAA activated the hippocampal CA3 neurons of Wistar rats via the metabotropic glutamate receptor (mGluR) in acutely dissociated hippocampal CA3 neurons. The mechanism of NAA action on CA3 neurons was examined with intracellular recording of Wistar and tremor rat hippocampal slices to evaluate the role of NAA in neuronal networks. Bath application of NAA (10 microM-1mM) dose-dependently induced depolarization in CA3 neurons of Wistar and tremor rats. Cadmium (a Ca(2+) channel antagonist) and GDEE (an ionotropic glutamate receptor antagonist) did not affect NAA-induced depolarization. Although ACPD (a nonspecific mGluR agonist) induced similar depolarizations in CA3 neurons, MCPG (a mGluR antagonist) inhibited NAA-induced depolarization. These results suggest that NAA probably activates hippocampal CA3 neurons via the mGluR in a neuronal network.

Morphologic features of human chorionic gonadotropin- or alpha-fetoprotein-producing germ cell tumors of the central nervous system: histological heterogeneity and surgical meaning.

Our study of germ cell tumors (GCT) of the central nervous system (CNS) investigated the relationship between tumor histology and patient serum titers of human chorionic gonadotropin (HGC) and alpha-fetoprotein (AFP). Thirty-five patients were enrolled. Their serum titers of HCG (mlU/ml) and/or AFP (ng/ml) before initial treatment were available, as were tumor specimens obtained before the administration of adjuvant therapy. They were divided into three groups, depending on whether HCG alone (group H), AFP alone (group A), or both HCG and AFP (group HA) were detected. Each group was subdivided into three groups: patients in group I had H, A, and/or HA titers below 9.9; patients in group II/III had titers from 10.0 to 999; and those in group IV had titers of 1000 or more. Serial sections of tissue specimens were repeatedly stained, mainly with hematoxylin and eosin (H-E) stain, HCG immunostain, and AFP immunostain. There were seven patients in the H-I group and five in H-II/III. Of these 12 patients, 11 had germinomas (G) and one had an embryonal carcinoma (EC). Five patients were included in group A: one was classified as A-II/III and had a germinoma, and the remaining four patients were in A-IV and had yolk sac tumors (YST) or mixed GCT consisting mainly of YST or EC (MXGCT-YST, EC). The HA group consisted of 18 patients. Three were classified as HA-I and had germinomas; nine HA-II/III patients had T or MXGCT-T; and six HA-IV patients had choriocarcinoma (CC), YST, MXGCT-CC, or MXGCT-YST. Throughout the study, the situations for the elevated serum titers could be elucidated in only four cases (three in group A-IV and one in group HA-IV). These results led to the conclusion that serologic evaluation is superior to morphologic evaluation in diagnosing marker-producing GCTs. From a diagnostic perspective, the role of surgery is to verify the HCG- and AFP-immunonegative tissue in patients with G, T, and EC.

Surgical treatment for intractable epilepsy caused by cavernous angioma in the temporal lobe of the dominant hemisphere--three case reports.

The surgical treatment modality for intractable epilepsy with cavernous angioma in the dominant hemisphere is still unclear. Three patients with medically intractable seizures associated with cavernous angioma in the dominant hemispheric temporal lobe underwent tailored resection based on magnetic resonance (MR) imaging, single photon emission computed tomography (SPECT), electroencephalography monitoring (from scalp and sphenoidal electrodes), and neuropsychologic assessment. Epileptogenic zones were located in the area surrounding the angioma in all patients and mesial temporal dysfunction in two patients. The adjacent cortex and gliotic tissues containing hemosiderin were resected, in conjunction with either total or partial resection of the nidus. Intraoperative electrocorticography (ECoG) was then performed. Additional resection of the mesial temporal structures or multiple subpial transection was performed as indicated by the ECoG findings. All three patients have been seizure free and showed no language or cognitive deterioration for 30, 18, and 14 postoperative months, respectively, while receiving tapered antiepileptic medication. Tailored resection based on electrophysiological data, MR imaging, SPECT, and intraoperative ECoG is effective for the treatment of medically intractable seizure associated with cavernous angioma in the temporal lobe of the dominant hemisphere.

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.

Subsidence of seizure induced by stereotactic radiation in a patient with hypothalamic hamartoma. Case report.

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.

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.

[A case of neurofibromatosis type I associated with basal meningocele and abnormal vessels].

A 21-year-old man with neurofibromatosis type 1 (NF 1) had many widespread cutaneous neurofibroma on his right face. Magnetic resonance imaging (MRI) revealed basal meningocele due to dysplasia of the skull base. Carotid and vertebral angiograms revealed occlusion of the right internal carotid artery, persistent primitive trigeminal artery. We have reviewed the clinical and radiographic features of this case of neurofibromatosis, meningocele and cerebral arterial abnormalities. NF associated with both intracranial vascular malformation and meningocele is very rare, and in our case both were thought to arise congenitally as a manifestation of mesodermal dysplasia. Careful follow up using MRI and MR angiography should be performed for such patients.

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.

Antiepileptic effects of 20-hydroxyecdysone on convulsive seizures in spontaneously epileptic rats.

We examined the effect of 20-hydroxyecdysone (20-HE), a neurosteroid found in insects that is involved in their developmental process, on both tonic convulsion and absence-like seizure in spontaneously epileptic rat (SER). When 20-HE was given orally to SER at 25-200 mg/kg, significant decreases of the tonic convulsion were observed with 100 and 200 mg/kg. Pretreatment of the animal with bicuculline (1 mg/kg, i.p.) antagonized the inhibitory effects of 20-HE. However, absence-like seizures were not affected by 20-HE. These findings indicate that 20-HE produces antiepileptic effects on tonic convulsion by acting on the modulatory site of GABA(A) receptors.

[A novel epilepsy animal model (NER)].

A mutant showing convulsive seizures spontaneously in a CJ: Wistar colony was named the Noda epileptic rat (NER). The NER exhibits tonic-clonic convulsion without any external stimuli once every 30 h. However, we succeeded in inducing similar convulsive seizures by applying priming sound stimuli (95 dB, 8 kHz, 30 sec) from 3 weeks of age in all 24 NER examined. When the effects of clinically available antiepileptics were tested on the seizures of such primed NER, the most potent agents were carbamazepine, diazepam, valproate, phenobarbital and trimethadione, while phenytoin and zonisamide showed lower potency. Furthermore, ethosuximide was not effective in inhibiting the seizures. In hippocampal slices of NER with convulsive seizures, repetitive firing accompanied by long-lasting depolarization was observed when a single stimulation was delivered to the mossy fibers in the CA3 pyramidal cell. This depolarization shift was completely blocked with a Ca2+ antagonist (nicardipine 10 nM). The long-lasting hyperpolarization that followed the repetitive firing was also observed with mossy fiber stimulation in the hippocampal CA3 pyramidal cells of the NER. These findings suggest that Ca2+ channel abnormality of the hippocampal CA3 pyramidal cells may be involved in the convulsive seizures.

Effect of antiepileptic drugs on absence-like seizures in the tremor rat.

We examined the effects of conventional antiepileptic drugs (AEDs) on absence-like seizures in homozygous tremor rats (tm/tm) to determine if they corresponded pharmacologically to human absence seizures and absence-like seizures in spontaneously epileptic rats (SER: zi/zi, tm/tm) with both tonic convulsive and absence-like seizures. Cortical and hippocampal EEG activity was recorded with chronically implanted electrodes. The effects of AEDS on seizures of the tremor rat showed profiles similar to those observed in human absence seizures and also in absence-like seizures of SER. The absence-like seizures, associated with paroxysmal bursts of 5-7-Hz spike-wave complexes, were inhibited by trimethadione (TMO 200 mg/kg intraperitoneally, i.p.), ethosuximide (ESM 100 and 200 mg/kg, i.p.), valproate (VPA 100 mg/kg, i.p.), and phenobarbital (PB 10 and 20 mg/kg, i.p.). Phenytoin (PHT 20 mg/kg, i.p.) was ineffective. These results are consistent with the conclusion that the tremor rat is a useful model for evaluating new AEDS for human absence seizures.

[A case of pituitary adenoma with simultaneous secretion of TSH and GH detected by double immunostaining method].

A rare case of simultaneous hypersecretion of thyroid stimulating hormone (TSH) and growth hormone (GH) in a pituitary adenoma is reported. A 59-year-old male complaining of general fatigue, dyspnea on exertion and finger tremor was admitted. Examination on admission, he revealed with hyperthyroidism and hypersecretion of TSH and thyroid hormones. Administration of TRH did not further increase serum TSH level, and administration of T3 also had no effect on TSH secretion. CT scan showed a pituitary macroadenoma 13mm in diameter. MRI demonstrated a homogenously hypointense mass with Gd-DTPA enhancement in the left side of the sella turcica. The entire chromophobic adenoma was removed by trans-sphenoidal surgery. Immunostaining of the specimen showed that the cytoplasm of the adenoma cells was positive for both TSH and GH. Double immunostaining using avidin-biotin-peroxidase complex (ABC) method and immunogold silver staining (IGSS) method, showed that the adenoma cells had been secreting both GH and TSH at the same time. After the adenomectomy, the hyperthyroidism disappeared, and all altered indicators of pituitary function returned to normal.