Effects of vitamin E (DL-α-tocopherol) on the growth inhibition, the inhibition of colony formation, and the morphological change of three rat glioma cell lines (RG-12, C-6, and 9L cells) were evaluated in tissue culture. Moreover, the combined efficacies of vitamin E and several chemotherapeutic agents on the survival fraction of 9L glioma cells were studied using the colony-forming assay. Significant growth inhibitory effects appeared with the addition of vitamin E to three rat glioma cell cultures, with dose-dependency at concentrations ranging from 5 to 50 μg/ml of vitamin E. Effective dose (ED50) was 15 μg/ml for RG-12 cells, 17.2 μg/ml for C-6 cells, and 28.0 μg/ml for 9L cells. Regrowth curve analysis of glioma cells following 48 hour administration of vitamin E showed reversible change in growth of glioma cells. The addition of vitamin E to the exponentially growing cultures caused morphological changes in glioma cells, which became visible as early as 24 hours after its administration. The glioma cell processes treated with vitamin E became more elongated than those of untreated cells. Colony-forming assay for evaluation of the combined efficacy of vitamin E and several chemotherapeutic agents showed a significant synergistic effect of vitamin E on the cytotoxicity of vincristine sulfate to 9L cells, which was also dose-dependent to vincristine sulfate and/or vitamin E concentrations (P<0.01). Vitamin E (20 μg/ml) showed only an additive effect on the cytotoxicities of ACNU, bleomycin, and 5-fluorouracil to 9L cells. In conclusion, vitamin E showed a significant synergistic effect on the cytotoxicity of vincristine sulfate to 9L cells. Although the mechanism of this synergistic effect was unknown, more detailed in vitro and in vivo analyses should prove useful in the treatment of malignant gliomas with vitamin E.
A comparative study was made of the capsular vessels of acute subdural hematoma in its chronic healing stage and those of chronic subdural hematoma. In acute subdural hematoma in the chronic healing stage, the capsular vessels were formed secondary to hematoma. Microscopically, they were often streamlined with perivascular lymphocytic cuffings. They had scant blood components and demonstrated almost no perivascular hemorrhage. Electronmicroscopically, the endothelial cells were thick with numerous swollen mitochondria, enlarged rough endoplasmic reticula and free ribosomes. The capsular vessels seemed to be tight, as the endothelial cells were coated by fibrinoid material and had numerous tight junctions. In the chronic subdural hematoma, the capsular vessels or sinusoids were formed preceding hematoma. Microscopically, their lumina showed balloon-like enlargement and were surrounded by flattened endothelial cells. They had both perivascular hemorrhage and accumulation of various inflammatory cells. Electronmicroscopically, the endothelial cells were thinner and some had clear cytoplasms. Most characteristic was the frequency of endothelial gap junctions. The sinusoids seemed to be fragile, playing an important role in the enlargement of this hematoma.
As a simple and practical method to measure cerebellar dysfunction, finger tapping was quantitatively analysed with the use of an 8 bit micro-computer. The subject was asked to tap with the index finger on the calibration switch of a conventional EKG apparatus for 30 sec with their best tempo and rhythm. The switch was connected to a micro-computer which measured the tapping interval and calculate their average (I) and standard deviation (SD). The SD was further standardized by a percentage of the average interval ((SD/I)×100 = SD%). These parameters were displayed on a TV-monitor and were recorded on a line-printer and on magnetic tape. This test was applied to three groups of subjects: 111 normal subjects, seven patients of cerebellar hemorrhage, and 18 patients of parkinsonism. In normal subjects, I was 172.9 ± 29.3 msec and SD was 13.3 ± 10.6%. In cerebellar hemorrhage patients, I = 337.4 ± 85.7 msec and SD = 34.6 ± 29.9%, while in parkinsonism patients, I = 414.5 ± 284.7 msec and SD = 12.1 ± 11.4%. The correlation between I and SD was statistically analysed. Differences were significant between all three groups. In summary, this test was simple and effective for the quantitative and chronological analysis of cerebellar function.
Air CT cisternography was performed by collecting a small amount of air, introduced by lumbar puncture, in the cerebellopontine angle cistern, and when combined with target imaging, this technique enabled high spatial resolution. Eight patients clinically suspected of having small acoustic tumors were evaluated by this method. Air CT cisternogramy outlined four small tumors, three of which had not been demonstrated by intravenous contrast-enhanced scan. One tumor was totally intracanalicular. The VIIth and VIIIth cranial nerves were well demonstrated in the cerebellopontine angle cistern. Side effects of this technique were headache, nausea, or vomiting. Air CT cisternography was the method of the choice in the neuroradiological diagnosis of small and intracanalicular acoustic tumors.
Fifty-seven cases of primary intracranial germ cell tumors seen at the Hokkaido University Hospital from 1962 to 1980 were reviewed with special reference to local recurrence and spinal metastasis. The 57 tumors consisted of 47 germinomas (15 histologically verified and 32 histologically non-verified), 4 teratomas, and 6 teratoid tumors. This series comprised 49 males and 8 females, with ages ranging from 5 to 41 years (mean 18.1 years). Tumors were mainly treated with conservative therapy (cerebrospinal fluid shunting and radiotherapy) and only 11 tumors were treated with direct surgical removal. The 1-year survival rate of 47 cases of germinoma was 89%, 5 year survival 82%, and 10 year survival 76%; whereas the 5-year survival rate of teratomas and teratoid tumors was 44%. In teratomas, radiotherapy was not effective and long-term survival was obtained after surgical removal. Of the 15 fatalities, four died of tumor recurrence and two died of spinal metastases. Seven (12.3%) of the 57 patients had tumor recurrence. Of the seven patients, the recurrence incidence was four teratomas and teratoid tumors compared with three germinomas. Another seven patients (12.3%) had spinal metastases; of these, six had germinomas. Spinal metastasis developed within six months of the initial treatment. These patients were treated with laminectomy and irradiation to the spinal axis after the metastases developed. Three can accomplish self-care. Differential diagnosis of intracranial germ cell tumors was possible by CT, CSF cytology, and measurement of alpha-fetoprotein and human chorionic gondotropin without biopsy. A plan of management was proposed based on pathological features: Radiation therapy with or without shunting operation should be the primary treatment for germinomas. Moderate doses of irradiation (4, 500-5, 000 rads) would be adequate to control tumor in germinomas. Prophylactic irradiation of the whole spinal axis is necessary for certain types of germinomas. Direct operation should be chosen in teratomas and teratoid tumors. Postoperative radiotherapy and chemotherapy are necessary for the treatment of teratoid tumors.
Shunt function tests were carried out 52 times in 32 cases of suspected malfunction of ventriculoperitoneal or ventriculoatrial shunt. Shunt function tests consisted of radioisotope (RI) study (flow study and shuntgraphy), CSF pressure measurement, and infusion test. The first was performed in all cases, the second in half, and the last in eight. In the majority of the cases it was not enough to evaluate the shunt function by RI study alone as about 45% of the 21 cases which showed an abnormal flow pattern and abnormal shuntgraphy were found either by surgery or infusion test to actually have patent shunt systems. Such cases were regarded as false positive. All of the three cases which showed abnormal delayed flow pattern and high CSF pressure (above 150 mmH2O) were found by surgery to have shunt blockage. In addition to RI study, measurement of CSF pressure in the valve was necessary to correctly evaluate shunt functioning. Nine cases which showed delayed flow pattern and low or normal CSF pressure were classified by surgery and/or infusion test into two groups, i.e. the shunt-obstructed group (3 cases), and the shunt-patent group (6 cases). As the opening pressure of the shunt system was revealed by the infusion test, this test was very important in evaluating shunt patency for these cases.
The authors experienced 14 operative cases with moyamoya disease (3 children and 11 adults). Presenting symptoms were hemorrhagic attack alone in 6 cases, hemorrhagic attack and ischemic episode at different times in 2 cases, and ischemic attack alone in 6 cases. Out of 14, 12 subjects underwent bilateral operations and 2 were operated unilaterally. In total, 26 sides were operated and operative methods consisted of superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis alone in 11 sides, STA-MCA anastomosis with encephalo-myo-synangiosis (EMS) in 6 sides, and EMS alone in 9 sides. Encephalo-arterio-synangiosis (EAS), named by the authors, was performed in 2 cases as a supplementary operation. Follow-up periods ranged from 1 to 44 months (average 24 months). Outcomes were “excellent” in 9, “good” in 4, “good” followed by “dead” in one. Out of 8 subjects who presented hemorrhagic attack before the operation, 2 cases showed another minor hemorrhagic attack 30 months and 31 months, respectively, following STA-MCA anastomoses. The relationship between absence of reduction of moyamoya vessels following surgery and repeated bleeding, and the surgical indication for the hemorrhagic type were discussed. STA-MCA anastomosis with EMS (and EAS) seemed to be the most preferable operative method at present.
Between September 1971 and December 1982, 623 patients were admitted for treatment of cerebral aneurysms. Of these patients, there were 10 whose initial panangiography showed negative findings for bleeding. The aneurysms were subsequently revealed by repeat angiography in 8 patients and by autopsy in 2. The location of the aneurysm was the anterior communicating artery in 5 patients, the middle cerebral in 3, and the internal carotid in 2. The size of the aneurysm, when detected, was small: the average was 3.0 mm in length and 2.5 mm in diameter. The possible causes of diagnostic error at the initial angiography were thought to be: severe vasospasms in 1 patient, inadequate projections in 4, films of poor quality in 2, ruptured aneurysm overlooked in patients with multiple aneurysms in 2, and no distinct evidence of aneurysm even in retrospect in 1. The clinical grade after Hunt and Hess on admission was Grade I in 2 patients, Grade III in 4, Grade IV in 3, and Grade V in 1. The clinical outcome was excellent in 3 patients, good in 2, poor in 1, and dead in 4. The patients who became poor had had diffuse, severe vasospasms and demonstrated cerebral infarction in the regions supplied by the involved arteries. One patient had experienced a second bleeding before the correct diagnosis was achieved.
A case of an anterior communicating artery aneurysm associated with bilateral middle cerebral artery occlusion was reported. A 62-year-old female was admitted because of severe headache and disturbance of consciousness for 4 hours. She had a past episode of numbness of the left fingers and lips and a history of hypertension and diabetes mellitus. Computed tomography revealed subarachnoid hemorrhage and a small low density area, a probable old infarction. Cerebral angiography showed an anterior communicating artery aneurysm associated with bilateral middle cerebral artery occlusion. Distal parts of the bilateral middle cerebral arteries were visualized by the collateral blood flow through leptomeningeal anastomoses mainly from the anterior cerebral arteries and less from the posterior cerebral arteries. The aneurysm was located at the left A1-A2 junction where the hemodynamic stress due to the well-developed collateral circulation might have been great. This case indicated that the hemodynamic stress complicated with hypertension, aging, and/or diabetes mellitus might play an important role in the development and rupture of cerebral aneurysms.
The biological characteristics of primary intracranial malignant lymphoma have not been fully understood in comparison with systemic malignant lymphoma. The authors presented 3 cases of verified intracranial malignant lymphoma which showed peculiar findings in the postoperative follow-up CT scans and evident alteration of histological features. Results of immunological examination of these tumors were different in each case; one was of non-T non-B type, another was B-cell type, and the third was negative. The most interesting finding from CT follow-up was that two tumors showed spontaneous regression of the high density mass lesions and recurrence in remote areas. Though not all of the CT lesions could be subjected to exploration, all surgical specimenes were verified as primary intracranial malignant lymphoma. Beside multiplicity of the tumors during follow-up, the size and the shape of the tumors often changed, and histological transformation was confirmed in one case.
The patient, a 15-year-old female, was admitted because of occipitalgia of one year's duration. CT scan revealed contrast enhancement resembling tuberculous meningitis or pineal region tumor in the cisterns of the skull base as well as in the pineal region. Cytological examination of the CSF showed clusters of atypical cells and brain tumor was suspected. Intrathecal injection of ACNU and radiotherapy showed some effect on neurological and CT scan findings, but the enhancement in the cisterns again gradually increased in size. The clinical course was downhill and the patient expired 2 years after admission. Autopsy revealed diffuse proliferation of atypical astrocytic cells consistent with astrocytoma Grade II in the leptomeninges of entire central nervous system. No gliomatous changes were noted in the brain and spinal parenchyma, and the diagnosis of primary diffuse leptomeningeal gliomatosis was made. Primary leptomeningeal gliomatosis is rare and only 16 cases are reported in the literature. The diffuse form especially rare and this was the fourth case, so far reported.