Shigeru Tsunoda

Frontal midline theta rhythms reflect alternative activation of prefrontal cortex and anterior cingulate cortex in humans

Frontal midline theta rhythm (Fm theta) often appears on electroencephalogram (EEG) during consecutive mental tasks. To clarify the source of rhythmic activity, magnetoencephalogram (MEG) and EEG were simultaneously measured in six healthy volunteers during different mental tasks using whole head MEG system. MEG records were averaged every one cycle of Fm theta rhythms using individual positive peaks of Fm theta waves in Fz EEG as a trigger. Averaged theta components of MEG signals were analyzed with a multi-dipole model. Two sources were estimated to the regions both of the prefrontal-medial superficial cortex and anterior cingulate cortex (ACC). These regions were alternatively activated in about 40 to 120 degrees phase shift during one Fm theta cycle. From above results, we hypothesize that appearance of Fm theta during consecutive mental tasks reflects alternative activities of the medial prefrontal cortex and ACC.

Analysis of prognostic and survival factors related to treatment of low-grade astrocytomas in adults.

Prognostic factors for low-grade astrocytomas have been proposed, but optimal treatment remains controversial. Eighty-eight consecutive adult patients with supratentorial low-grade astrocytomas were retrospectively reviewed to determine specific factors influencing outcome. All underwent craniotomy (43 radical resections, 45 nonradical resections). Sex, age at diagnosis, preoperative Karnofsky performance status (KPS), tumor location, estimated extent of resection, radiation, chemotherapy, histological type, p53 status, MIB-1 staining and the apoptotic index were assessed as parameters for prognostic significance. KPS (p = 0.03), tumor location (p < 0.001), extent of surgical resection (p < 0.001) and radiotherapy (p = 0.01) were significantly assoicated with longer survival rates by univariate analysis. Multivariate analysis also showed a significant correlation between radiation therapy after surgical removal and survival time (p < 0.001). p53 status was not of importance in determining the necessity for radiotherapy. Radical surgical removal is the most important factor in the management of low-grade astrocytomas. Radiation therapy appears to be effective in improving the prognosis regardless of the extent of surgical resection or the p53 status.

Cytokine-induced enhancement of calcium-dependent glutamate release from astrocytes mediated by nitric oxide

Cytokines are produced in the central nervous system (CNS) and exhibit various effects on neurons, microglia, and astrocytes. Astrocytes can release chemical transmitters, including glutamate, in a calcium-dependent manner, which may mediate communication between neurons and astrocytes. To date, no studies have been conducted on the effects of cytokines on calcium-dependent glutamate release from astrocytes. Here, we studied the effects of cytokines on calcium-dependent glutamate release. Cytokines enhanced glutamate release and induced the expression of inducible nitric oxide synthase (iNOS) and the production of nitric oxide (NO). The inhibition of iNOS eliminated the cytokine-induced enhancement of glutamate release, and treatment with a NO donor, even in the absence of cytokines, increased glutamate release. Thus, cytokines enhance glutamate release, and this enhancement is mediated by NO.

The spectrum of malignancy in craniopharyngioma.

Craniopharyngiomas are low-grade epithelial neoplasms occurring almost exclusively in the sellar/suprasellar region. Histologic malignancy is extremely rare; the literature consists mostly of isolated case reports. Herein, we report 3 patients with craniopharyngiomas exhibiting histologic malignancy, 2 of which received radiation therapy before its appearance. Hematoxylin and eosin-stained slides and selected immunohistochemical stains were reviewed in all cases. Microvessel density analysis was performed in case 2. The patients included 2 men and 1 woman, age 14, 31, and 58 years at presentation, respectively. All patients expired 3 months to 9 years after first resection and 3 to 9 months after identification of histologic malignancy. The latter developed after multiple recurrences and radiation therapy in 2 cases, but seemed to arise de novo in 1 case resembling odontogenic ghost cell carcinoma and lacking any definite low-grade craniopharyngioma precursor. The malignant component of the other 2 cases resembled squamous cell carcinoma and low-grade myoepithelial carcinoma, respectively. The MIB-1 labeling index was markedly increased in the malignant component in comparison with the low-grade precursor. Malignant transformation in craniopharyngiomas, although rare, does exist. It assumes varied histologic appearances, usually after multiple recurrences and radiation therapy, and has a near uniformly fatal outcome. De novo malignancy in odontogenic tumors of the sella is even more unusual, but also has an ominous prognosis.

Clinical studies of de novo aneurysms.

Although multiple cerebral aneurysms ae well recognized, a new aneurysm has only rarely been documented after successful treatment for an aneurysm elsewhere. In our consecutive series of 986 patients with intracranial saccular arterial aneurysm collected from 1975 to 1990, nine patients who had previously unverified (hence, de novo) intracranial aneurysms and ruptures at intervals of 4 to 7.5 years after clipping of an initial aneurysm are presented here. All nine had undergone successful treatment of a previous aneurysm; preoperative and postoperative angiography showed not only successful clipping of the first aneurysm but also no incidence of multiple aneurysms. These patients had suffered from hypertension before their second admission. Seven of the nine patients were treated surgically. All patients had experienced angiographical or symptomatic vasospasm after the first subarachnoid hemorrhage. In the second admission however, seven patients who underwent the surgery for a new aneurysm suffered from no vasospasm in spite of the prominent second subarachnoid hemorrhage. Two of the nine patients died of primary brain damage due to the hemorrhage and underwent necropsy. A histological study of a new aneurysm demonstrated the same findings as that of a usual saccular aneurysm. This clinical study of our patients suggests that it is important to control blood pressure for protection against a new aneurysm formation.

Selective vulnerability to radiation in the hippocampal dentate granule cells.

BACKGROUNDnRadiation therapy is an effective approach in the treatment of highly radiosensitive brain tumors such as germinomas. However, recent studies have reported intellectual disturbances in patients who underwent whole-brain irradiation as children. We detected apoptosis in the infantile murine cerebrum after systemic X-ray irradiation.nnnMETHODSnSubjects were 100 ICR mice 4 weeks old, of which 90 were systemically exposed to 18 Gy X-rays (0.45 Gy/min); 10 each were decapitated and the cerebrums were removed 1, 3, 6, 9, 12, 18, 24, 48, and 72 hours after irradiation. Controls were 10 unirradiated mice. DNA fragmentation analysis was carried out by agarose gel electrophoresis, and morphological analysis was by the TUNEL method.nnnRESULTSnAccording to agarose gel electrophoresis, the cerebral DNA ladders were detected only over 6 to 24 hr, peaking in 9 hr. Even at the peak, band intensity was nearly double that of the unirradiated normal thymus. According to the TUNEL analysis, radiation-induced apoptosis increased, with a peak at 9 hours, but decreased 24 hours after irradiation. Apoptotic cells were always localized exclusively in the hippocampal dentate granule cells.nnnCONCLUSIONSnWe found that vulnerability to radiation existed in the hippocampal dentate granule cells. Intellectual disturbances in patients who have undergone whole-brain irradiation may be caused by injury to the hippocampus.

Management of dissecting aneurysms of the posterior circulation

SummaryWe analysed the clinical presentation, treatment and outcome of our own 36 cases of posterior circulation dissecting aneurysms (DA) and discussed the surgical indications and procedures regarding posterior fossa DA. Twenty one cases were male, 15 cases were female. Their mean age was 54±14 years. Clinical manifestations were subarachnoid haemorrhage (SAH) in 14 cases (39%) and ischaemic attacks in 22 cases (61%). Three of 14 SAH cases had rebleeding in the acute stage. Angiographic findings were aneurysmal dilatation in 16 cases, retention of contrast medium in 12 cases, string sign in 9 cases, double lumen in 4 cases, pearl and string sign in 3 cases, and occlusion of parent artery in 2 cases. Surgical treatment was performed on nineteen cases (53%). The operation was carried out in the acute stage on the SAH group; in the subacute or chronic stage on the ischaemic group. The surgical procedure was the proximal ligation, trapping and removal of DA with or without revascularization of the parent artery. 84% of the surgically managed patients and 71% of the nonsurgical cases had a favourable outcome (good recovery or moderate disability). Poor prognosis was revealed from the rebleeding and primary neurological stage. We recommend surgical treatment in the acute stage on the SAH group. On the ischaemic group surgical treatment in the subacute or chronic stage is recommended, if the DA has the risk of rupture or progression of the dissection.

Secretory meningioma with elevated serum carcinoembryonic antigen level

We recently encountered a 68-year-old woman with right sphenoid wing meningioma of the secretory type accompanied by an elevated serum carcinoembryonic antigen level. This case was neuroradiologically characterized by marked brain edema. Histologically, the lesion was rated as having meningothelial components and was rich in blood vessels and pseudopsammoma bodies. Carcinoembryonic antigen, epithelial membrane antigen, keratin, and cytokeratin were immunohistochemically detected in the pseudopsammoma bodies and the cells producing these bodies.

The influence of the calcium antagonist nimodipine and induced hypertension on the behavior of the cerebral pial arteries, the blood-brain barrier, cerebral edema, and cerebral infarction in cats with one-hour occlusion of the middle cerebral artery

Thirty anesthetized cats were randomly assigned to one of three groups of 10 cats each: nimodipine treatment, nimodipine treatment combined with induced hypertension, or a control group. The behavior of the cerebral pial arteries was measured by means of microscopic observation through a cranial window. The middle cerebral artery of each cat was clipped for 1 hour via the transorbital approach. Five hours after circulation was reestablished in the middle cerebral artery, Evans blue dye was injected intravenously: 30 minutes later, the animal was killed. Administration of nimodipine or saline in the treated or control group was started 5 minutes before the middle cerebral artery was clipped and maintained until the end of the experiment. Induced hypertension was produced by administration of dopamine during the occlusion. Damage to the blood-brain barrier (BBB) was judged by extravasation of Evans blue dye. Cerebral edema and infarction were evaluated from histological findings. They were most prominent in the control group: the extent of hemisphere affected was as follows (mean +/- standard error): extravasation, 40.5 +/- 8.8%; edema, 43.2 +/- 5.7%; infarction, 35.5 +/- 9.6%. On the other hand, the extravasation of Evans blue dye and cerebral edema were significantly more extensive in the group treated with nimodipine and induced hypertension (extravasation, 28.2 +/- 9.6% of the hemisphere; edema, 30.3 +/- 7.1%) than in the group treated with nimodipine alone (extravasation, 18.5 +/- 8.7% of the hemisphere; edema, 19.4 +/- 6.3%), but the infarction size was similar in both groups (16.6 +/- 4.9% of the hemisphere in the former; 17.0 +/- 6.2 in the latter).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of repeated temporary clipping of the middle cerebral artery on pial arterial diameter, regional cerebral blood flow, and brain structure in cats.

Temporary clipping of the major arterial trunk is an important maneuver to control excessive unexpected bleeding in neurosurgical operations; however, repeated temporary clipping can give rise to severe neurological deficits after surgery. The present study was performed to confirm and explain these clinical findings. Initially, a single 20-minute or 1-hour occlusion of the middle cerebral artery was performed in each of 5 cats. Pial arterial diameter was determined by video imaging, regional cerebral blood flow was measured by autoradiography, and cerebral edema and infarction were observed. In the 20-minute occlusion group, no abnormal changes were found 5 hours after recirculation. In the 1-hour occlusion group, pial arteries were dilated by 45%, and regional cerebral blood flow increased to more than twice the resting cortical values. The extent of cerebral edema was 41.2 +/- 7.5% (SE) and infarction was 34.5 +/- 9.5% (SE) of the hemisphere. In the second experiment, three 20-minute occlusions of the middle cerebral artery in a 1-hour interval were performed in 20 cats. In 10 of them, thiopental (40 mg/kg) was used to protect the brain. In the group without barbiturate treatment, pial arteries were dilated by 40% at the end of experiment, regional cerebral blood flow decreased to about 70% compared with single 20-minute occlusion, cerebral edema was 19.5 +/- 8.1% (SE), and infarction was 8.1 +/- 3.7% (SE) of the hemisphere. In the treated group, these were only trivial changes. The effect of repeated clipping may cumulatively cause brain damage, and barbiturates should be used whenever repeated clipping is necessary.