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Yasuo Suzuki and Ryuichi Tanaka

✓ Carcinoembryonic antigen (CEA) in plasma, cerebrospinal fluid (CSF), and tumor cyst fluid obtained from patients with a variety of intracranial tumors was determined by radioimmunoassay. Slightly elevated levels of plasma CEA, ranging from 2.6 to 3.8 ng/ml, were noted in six (4%) of 161 patients with primary brain tumors: in three gliomas, two pineal tumors, and one acoustic neurinoma, respectively. On the other hand, 17 (37%) of 46 patients with metastatic brain tumors showed a definite elevation, and most of them had values higher than 5.0 ng/ml. Of 37 patients with primary brain tumors, only one with a pineal germinoma showed a significant elevation of CEA in CSF, whereas eight (44%) of 18 patients with metastatic brain tumors showed high values of CEA in CSF. All six patients with leptomeningeal carcinomatosis showed elevated CEA in CSF. Levels of CEA in tumor cyst fluid were determined in 17 patients with intracranial tumors, including 12 gliomas, two craniopharyngiomas, two metastatic tumors, and one meningioma; elevation of CEA in tumor fluid was noted in two craniopharyngiomas and one metastatic tumor. Sequential determination of CEA in plasma or CSF revealed that the CEA levels were well correlated with the activity of brain tumors. Consequently, the determination of CEA in plasma or CSF is valuable for the differential diagnosis between primary and metastatic brain tumors and for the management of CEA-producing tumors.

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Akira Watanabe, Ryuichi Tanaka, Norio Takeda and Kazuo Washiyama

✓ The relationships between distribution of deoxyribonucleic acid (DNA)-synthesizing cells (S-phase cells) and blood flow and glucose utilization were investigated in rat brain tumors using an autoradiographic technique and immunoperoxidase staining for bromodeoxyuridine (BUdR). Two strains of rat brain tumor were used: strain A and B, both induced by the Rous sarcoma virus. Strain A was biologically more malignant than strain B. The blood flow was unevenly distributed in the tumor; compared with the contralateral cortex, the average blood flow in the tumor was about 50% in strain A and 60% in strain B. The distribution of blood flow did not correlate with the distribution of S-phase cells or with the distribution of vessels in the tumor in either strain A or B. The average glucose utilization in strain A was about 250% and in strain B about 170% of that of the contralateral cortex. The high glucose utilization area correlated well with the distribution of BUdR-positive nuclei in strain B. These findings suggest that the biological malignancy of a tumor correlates with glucose utilization rather than with blood flow, and that malignant brain tumors show a marked increase in glucose utilization for nucleic acid synthesis.

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Kenichi Nishiyama, Hiroshi Mori and Ryuichi Tanaka

Object. The aim of this study was to analyze physiological changes in cerebrospinal fluid (CSF) dynamics following endoscopic third ventriculostomy (ETV) for shunt-dependent noncommunicating hydrocephalus.

Methods. Clinical data obtained in 15 patients treated with ETV for shunt malfunction were analyzed. Magnetic resonance imaging studies demonstrated the obstruction of the ventricular system preoperatively. After ETV, the existing shunt system was removed and a continuous extraventricular drain, set at 30 cm H2O in height, was installed to measure daily amounts of CSF outflow. Cerebrospinal fluid dynamics after ETV were also evaluated using 111In-diethylenetriamine pentaacetic acid radioisotope cisternography in six of 15 patients within 1 month of the procedure. Three patients underwent cisternography at 6 months after ETV. Cisternograms were obtained at 1, 5, 24, and 48 hours after injection of the radioisotope. To study CSF absorptive capacity, ratios of radioisotope counts at 48 and 5 hours after injection were calculated (C48:C5). Seven of 15 patients had daily outflows of CSF of less than 20 ml; this volume decreased quickly within a few days. The other eight patients demonstrated an outflow of more than 150 ml of CSF for several days, three of whom had signs of transiently increased intracranial pressure. Their CSF outflow volume decreased gradually and symptoms improved within 1 week. Ratios of C48:C5 were within normal limits in five of six patients who had undergone cisternography 1 month after ETV. These ratios were decreased in all three patients who had undergone cisternography at 6 months after ETV compared with that measured at 1 month after the procedure.

Conclusions. Our data suggest that CSF dynamics convert from a shunt-dependent state to a shunt-independent state within 1 week following ETV in patients with shunt-dependent noncommunicating hydrocephalus. Nonetheless, intraventricular pressure does not decrease quickly in certain cases. Cerebrospinal fluid absorptive capacity or CSF circulation through the subarachnoid space may show further improvement several months after ETV.

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Takatoshi Sorimachi, Hiroshi Abe, Shigekazu Takeuchi and Ryuichi Tanaka

Object. The purpose of this study was to investigate the possibility of preventing cumulative neuronal damage after repetitive severe ischemia.

Methods. The authors monitored ischemic depolarization in the gerbil hippocampus, which has recently been shown to be a good experimental model of the effects of brief ischemia on the brain, and evaluated neuronal damage in the CA1 subregion 7 days after the ischemic insult. In a single-ischemia paradigm, the results indicate that induction of ischemia-induced neuronal damage depended on the duration of ischemic depolarization. Neuronal damage can be detected in the CA1 subregion after a period of depolarization lasting 210 seconds. Using a double-ischemia paradigm in which the animals were subjected to two periods of ischemia, there was apparently no accumulation of neuronal damage from the first ischemic episode to the second, provided the duration of the first period of ischemic depolarization did not exceed 90 seconds. Neuronal damage accumulated when the duration of the first ischemia episode exceeded 90 seconds, regardless of the duration of the reperfusion interval between the two ischemic insults. Finally, when the ischemic insult was spread over four separate episodes, each lasting 90 seconds (with a reperfusion interval of 5 minutes), neuronal damage was not found when the total depolarization period was less than 420 seconds.

Conclusions. The authors conclude that cumulative neuronal damage may be avoided by adopting an intermittent ischemia approach. The implications of these results for human surgery requiring temporary occlusion of the cerebral arteries are discussed.

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Osamu Sasaki, Tetsuo Koike, Ryuichi Tanaka and Hiroshi Ogawa

✓ A case of subarachnoid hemorrhage (SAH) from a dissecting aneurysm of the inferior limb of the middle cerebral artery is reported. The patient's clinical status and the initial and follow-up angiographic appearance of the aneurysm are presented. Diagnosis and treatment are briefly discussed. It is suggested that, if angiography demonstrates luminal narrowing or vascular occlusion in a patient with unexplained SAH, a dissecting aneurysm of the carotid system should be considered as a cause of the hemorrhage.

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Takatoshi Sorimachi, Hiroshi Abe, Shigekazu Takeuchi and Ryuichi Tanaka

Object. The authors investigate whether depolarization monitoring is an accurate index of ischemic damage in a gerbil model of unilateral ischemia and assess the effects of brief cerebral ischemia on protein synthesis in this model.

Methods. The authors evaluate the relationship between the duration of ischemic depolarization caused by unilateral carotid artery occlusion and ischemia-induced neuronal damage in the CA1 subregion 7 days after ischemia. When the depolarization period exceeded 210 seconds, some neuronal damage was detected, and almost complete neuronal damage was observed when the period exceeded 400 seconds. Uptake of [14C]valine was evaluated in ischemic and nonischemic CA1 subregions. Disturbances in protein synthesis were seen in all animals subjected to sublethal ischemia (≤ 210-second depolarization) after a 10-minute recirculation, and after 2 and 6 hours of recirculation in animals with 90 seconds or more of depolarization. Inhibition of protein synthesis was proportional to the length of the depolarization period. After 1 and 3 days of recirculation, protein synthesis returned to near normal, and some animals with depolarizations greater than 180 to 210 seconds showed an increase in protein synthesis. Protein synthesis in all animals returned to normal levels after 7 days of recirculation.

Conclusions. In this study the authors demonstrate that monitoring of ischemic depolarization is a useful method to predict neuronal damage in the hippocampal CA1 in this model, and they identify subtle changes in protein synthesis after brief ischemia. Sublethal ischemia was divided into three categories by its depolarization period (< 90 seconds, 90–180 seconds, and > 180–210 seconds) with regard to changes in protein synthesis.

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Osamu Sasaki, Hiroshi Ogawa, Tetsuo Koike, Takayuki Koizumi and Ryuichi Tanaka

✓ Five autopsied cases of dissecting aneurysms of the intracranial vertebral artery are reported and the literature is reviewed to clarify the clinicopathological correlations. In an autopsy series of 110 patients with subarachnoid hemorrhage (SAH), the incidence of this entity was 4.5%, with all five cases progressing rapidly to death from massive SAH. Cases of intracranial vertebral dissection can be divided clearly into two groups based on the clinical and pathological features. In the first group, the dissection is confined to the vertebral artery and a massive SAH develops caused by the rupture of the arterial wall. The plane of dissection is mainly subadventitial. In the second group, brain-stem infarction develops resulting from luminal occlusion by intramural hematoma. The plane of dissection is mainly subintimal, with the dissection extending to the basilar artery. The condition in the second group affects patients at a younger age. If the lesion is localized within the vertebral artery and does not extend to the basilar artery, the disease seems not to be fatal. The clinical features of the vertebral dissection are largely determined by the plane and extension of dissection. Vertebral artery dissection is due to many causative factors including hypertension, congenital or degenerative changes in the arterial wall, and anatomical and pathological characteristics of the vertebral artery.

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Seiichi Yoshida, Ryuichi Tanaka, Masashi Ono, Nobuyuki Takai and Takafumi Saito

✓ To ascertain whether tumor-specific immune response occurs in patients with malignant brain tumors, lymphocyte blastogenetic responses to tumor cells were examined in 18 patients prior to operation and other treatment. Among 12 patients with malignant glioma, the peripheral blood lymphocytes (PBL's) showed a positive blastogenetic response to their own glioma cells in seven (58.3%), whereas the tumor-infiltrating lymphocytes (TIL's) showed a positive response in only three (25%). In four (66.7%) of six patients with metastatic brain tumors, however, both the PBL's and TIL's showed a positive blastogenetic response to their own tumor cells. In these four patients, this lymphocyte blastogenetic response to tumor cells were at a much lower level compared with phytohemagglutinin P or allogeneic lymphocyte stimulation. Furthermore, these responses were increased when the cells were cultured with interferon-γ (500 U). Other lymphokines had no effect on the response. This method appears to be useful in identifying the tumor-specific immune response in patients with malignant brain tumor.

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Yukihiko Fujii, Shigekazu Takeuchi, Osamu Sasaki, Takashi Minakawa, Tetsuo Koike and Ryuichi Tanaka

✓ This study was undertaken to elucidate comprehensively the serial changes occurring in hemostatic systems after aneurysmal subarachnoid hemorrhage (SAH) and thereby to ascertain whether the examination of the integrity of these systems is helpful in predicting delayed ischemic neurological deficits (DINDs). The authors examined 117 patients admitted to the hospital within 24 hours after onset of SAH. Blood samples were collected from each patient on Days 0 (at admission), 3, 6, 14, and 30. A number of hemostatic parameters were examined in these samples, and the relationships between their changes and DINDs were assessed. Eighteen (15.4%) of the patients exhibited DINDs, and their frequency increased as the severity of subarachnoid clotting increased. Also, the frequency of DINDs was significantly higher in the patients with hydrocephalus on initial computerized tomography (CT) scans than in those without hydrocephalus. Regarding the hemostatic parameters at admission, there was no significant difference between the patients with and without DINDs. On Day 3, however, the fibrinogen and D-dimer levels were higher in the patients with than in those without DINDs. The fibrinogen and thrombin—antithrombin complex levels on Day 6 and the D-dimer level on Day 14 in the patients with DINDs were higher than the corresponding levels in those without DINDs. Multivariate analyses revealed that the following variables (in order of importance) were independent predictors of DINDs: the levels of D-dimer on Day 3, fibrinogen on Day 6, and the presence of hydrocephalus on admission. These data indicate that the levels of hemostatic parameters in concert with the CT findings may enable us to predict the appearance of DINDs.

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Osamu Sasaki, Ryuichi Tanaka, Tetsuo Koike, Akira Koide, Takayuki Koizumi and Hiroshi Ogawa

✓ The case of a patient presenting with dysphasic seizures due to a cavernous angioma coexisting with a venous malformation is reported. The cavernous angioma was resected with preservation of the venous malformation, as confirmed by postoperative studies. The patient was seizure-free following surgery.