Angiographic appearance of two cases of glioma of the lateral ventricle is reported. Angiographic features are: 1. the subependymal veins indicate asymmetrical dilatation of the lateral ventricle; 2. no evidence of mass lesions other than enlargement of the lateral ventricle; 3. the medial striate artery which normally supplies the cerebral parenchyma supplies the tumor; 4. the anterior choroidal and the lateral posterior choroidal arteries are not hypertrophic; and 5. the attachment of tumor to the walls of the lateral ventricle may be predicted by the feeding artery and the drainage veins.
Progressively rising intracranial hypertension reduces cerebral blood flow and cerebral vascular dilatation occurs during the advanced stage of intracranial hypertension. The rich adrenergic nerve supply of the cerebral vessels suggests that pressor amines possibly affect the cerebral circulation and the cerebral vascular tone. This study is to investigate the reactivity of norepinephrine and phentolamine on intracranial pressure (ICP) in patients with severe intracranial hypertension. Simultaneous recording of ICP and systemic blood pressure (SBP) was continuously made in 9 patients after the evacuation of intracerebral hematoma due to a ruptured intracranial aneurysm and hypertensive intracerebral hemorrhage. Severe intracranial hypertension due to brain swelling was observed in these patients. The trace of ICP revealed two patterns. One was that the mean ICP level was between 500-1000 mm H2O and the ICP curve were marked by transient and recurrent fluctuations. This pattern was seen in 5 patients. The other was that the mean ICP level exceeded 1000 mm H2O and the trace of ICP changes only with arterial pulse. This pattern was seen in 4 patients. Three stages were defined according to the reactivity of norepinephrine and phentolamine on ICP. In stage I, norepinephrine caused a transient decrease in ICP and phentolamine caused a rise in ICP. The trace of ICP in this stage showed transient and recurrent fluctuations. Stage II was marked by the absence of the ICP response to norepinephrine and phentolamine. During stage III, ICP changed depending on the variations of SBP after the administration of norepinephrine and phentolamine. The trace of ICP in stage II and III patients showed monotonous waves synchronous with arterial pulse. In terminal stage, this monotonous arterial pulse wave fell concomitant with SBP. The patients in stage I had a good chance to live if proper treatment, such as continuous ventricular drainage was carried out. The patients in stage II and III had a poor chance to live in spite of continuous ventricular drainage. There are varying degrees—in cerebrovascular dilatation accompanying intracranial hypertension. We have no information on the mechanism of this cerebrovascular dilatation at present. We speculate that the pressor amines such as norepinephrine may partly participate in the mechanism responsible for the vasodilatation. So, we attempted to grade the degree of this vasodilatation according to the reactivity to norepinephrine and phentolamine on ICP. It is presumed that cerebrovascular dilatation is slight and reversible in stage I patients, whereas cerebrovascular dilatation is profound and irreversible in stage II and III patients.
Studies on cerebral changes during recirculation after temporary ischemic insult were carried out in the Mongolian Gerbil which frequently shows anomaly of the circle of Willis. In this animal, occlusion of one side of the common carotid artery resulted in a large focal ischemia of the ipsilateral hemisphere in about 30%. Animals susceptive to ischemia could be selected by neurological symptoms observed soon after the carotid occlusion. Following temporary ischemia of 15, 30 mins., 1 hr., 3, 6 and 9 hrs., the cerebral circulation was resumed by releasing the carotid occlusion for different time lengths. A multidisciplinary and comparative approach which included a) histopathological study, b) morphological assessment on Blood-Brain Barrier (BBB) damage by Evans Blue for protein leakage and on edema, c) morphological evaluation of “no-reflow phenomenon” by injection of carbon black, d) contact autoradiographic assays on regional cerebral blood flow (rCBF) with 14C-antipyrine was made. 1. The histopathological change is related to the duration of ischemia and recirculation. The ischemic lesion appears to progress (or mature) after re-establishment of the circulation. The rate of “maturation” is related to the intensity of the ischemic insult, i.e. the shorter the occlusion time, the later the onset of tissue damage. Neuronal recovery was suggested by time course histological study. 2. The incidence and time of appearance of the BBB lesions following recirculation is related directly to the duration of the ischemic insult. When the duration of ischemia was 30 mins., BBB damage was demonstrated in 50% of animals only at 20 hours after re-establishment of the circulation. On the other hand, BBB damage was always seen in all animals at one hour after recirculation, when the duration of ischemia was 6 hours. 3. Although the duration of “no-reflow phenomenon” relates to the length of ischemia, the phenomenon is transient and lasts about 10 minutes in animals suffering from temporary ischemia up to 6 hours. 4. Following cerebral ischemia for one hour, bi-phasic, reactive hyperemia which includes oligemic phase in between was observed. Later hyperemia associates una voce with the appearance of severe tissue damage, which progressed continuously following release of carotid occlusion. The breakdown of BBB accompanied both severe tissue damage and local increase of rCBF. The histopathological changes as well as BBB damage for protein tracer appears and progresses concurrently after recirculation. Increased rCBF (luxury perfusion) was always noted when the tissue damage was severe.
Sequential changes of subarachnoid space after subarachnoid hemorrhage were studied in animal experiments by scanning electron microscopical observations. As a control study, the subarachnoid space of 14 dogs were observed with the scanning electron microscope. Then, 36 adult mongrel dogs underwent each direct injection of 1 ml/kg of fresh autogenous blood into the cisterna magna. Each of them was sacrificed at various periods ranging from immediately after to 6 months after the blood injection. Six dogs, sacrificed immediately after the blood injection, showed subarachnoid hematoma at the base of the brain without expansion to the parietal region. In these hematomas, fibrin fibers were already observed among the red blood cells. In all of 8 dogs sacrificed after 2-5 days of blood injection, subarachnoid clot was seen but no fibrosis had appeared. In 5 dogs after 7-9 days of blood injection, subarachnoid fibrosis in 4 and remaining clot in 2 were seen at this period. All of the 4 dogs killed after 2-3 weeks of the blood injection showed marked fibrosis or arachnoid thickening without remaining clot, and 3 of dogs sacrificed one month of the blood injection also showed subarachnoid fibrosis but normal findings were noted in the remaining 3. Moreover, even in 2 dogs which were sacrificed after 2 and 4 months respectively, marked fibrosis were observed. Those results suggested that the blood in the basal subarachnoid space disappears within 1-2 weeks and fibrosis occurs 1-3 weeks after the subarachnoid hemorrhage. And, in most cases, subarachnoid fibrosis which occurs in early period disappears by a month or so after the hemorrhage. In some cases, however, fibrosis or arachnoid thickening lasts for several months or more. The usefulness of scanning electron microscope to observe the subarachnoid space is emphasized.
It has been said that cerebellar symptoms caused by head injury are rare. The first reason is, injury of the cerebellum is usually fatal due to either combined intracranial hemorrhage or brain stem lesions. The second is, the posterior cranial fossa and cerebellum have specific features in anatomical view point so that the cerebellum rarely suffers from injury by impact. In 1969, R.C. Cantu reported on 2 cases which showed midline cerebellar symptoms consisting of dysarthria, truncal ataxia and rotatory nystagmus following occipital head trauma. He postulated a new syndrome “The transient traumatic cerebellar dysfunction” for this symptoms. We present 7 cases of post-traumatic cerebellar symptoms caused by closed head trauma. Summary of 7 cases : 1. Ratio of male and female was 5:2, age distribution was from 9 to 34 years of age; 2. Site of trauma included occipital region in 5 cases, frontal region in 1 case, and unknown in 1 case. Initial loss of consciousness was absent in 5 cases, few minutes in 1 case, and 2 weeks in 1 case; 3. Craniogram: 1 case showed right-frontal linear fracture and others were normal; 4. Cerebellar signs revealed were such as dysmetria, dysdiadochokinesis, horizontal nystagmus and ataxia. Other neurological findings such as pyramidal signs and sensory disturbances were negative; 5. Laboratory findings such as lumbar puncture and other pertinent findings were negative; 6. Clinical course: Cerebellar symptoms improved within few days or few months in 6 cases, whithin one year in 1 case; 7. Same symptoms reccurred twice in 1 case following minor occipital injuries. The symptoms were maximal immediately after trauma and steadily improved in all cases. The pathophysiology of these symptoms, whether it is due to cerebellar concussion or contusion, is unknown. In one case, traumatic infra-tentorial hematoma was suspected and suboccipital exploratory craniectomy was undertaken. However, neither hematoma nor contusion in the posterior cranial fossa and of the cerebellum, was discovered. The observations presented here and the cases reported by other authors suggest that these symptoms may occur with or without cerebellar hemorrhage and contusion. Because the authors experienced a recurrence of these symptoms in one patient as referred in 7., the authors presume that there must be some other predisposition in manifestation of this symptoms. Recognition of this symptoms is not only important but also helpful in the diagnosis of posterior fossa lesions after head injuries.
Patients with malignant tumor have immunological reaction to the tumor cells, but the reaction is suppresed with the growth of the tumor. For the clinical application of immunotherapy, the immunologic study of brain tumor patients is important. In this study we described the cell-mediated immunity and humoral immunity of brain tumor patients with special references to the pathological nature and clinical status. As for humoral immunity we detected tumor specific antibody against tumor cells by immunoadherence hemagglutination (IA) test (in 91 cases)and conducted quantitative analysis of IgG, IgM, IgA and, β1c/1A globulin by the immunodiffusion technique (in 35 cases) in patients' sera. Correlation between tumor specific antibody and IgM was studied by using the IA test. As for cell-mediated immunity we studied peripheral lymphocyte counts (in 140 cases) and tuberculin reaction (in 56 cases) before operation. Biopsied samples (in 208 cases) were examined for detection of infiltration crisis of lymphoid cells under the microscope. We also investigated lymphocytotoxic ability against tumor cells and the blocking effect of the patient's serum was detected by using the mixed lymphocytes-tumor culture method. The results are shown as follows : 1. High titer of the tumor specific antibody was always detected in serum of patients with glioma or sarcoma. This result suggested that the tumor specific antigen presented on the tumor cell membrane. 2. Essential components of the tumor specific antibody against brain tumor cells were detected in IgM fraction. 3. In malignant glioma and metastatic tumor, 40-60% of the patients showed lower than normal level of IgA and β1c/1A globulin. And 40-60% of the patients of benign glioma showed lower than normal level of IgM, IgA and β1c/1A globulin, whereas 50-75% of the patients of meningioma showed higher than normal level of IgG and IgA. 4. High percentage of malignant brain tumor patients showed lymphopenia (less than 1800/mm3), and negative tuberculin reaction which indicated depletion of cell-mediated immunity in these patients. The peripheral lymphocyte counts and tuberculin reaction was helpful to diagnose malignant tumor or benign tumor before operation, and also to evaluate prognosis of brain tumor patients. 5. Lymphoid cell infiltration in the tumor was found in 95% of metastatic tumors, 58% of meningiomas and 37% of gliomas. 6. Lymphocytes from glioma patients showed remarkable cytotoxic effect against glioma cells in mixed culture. Serum from the patients showed cytotoxic effect against tumor cells, although the effect was very poor compared with that of lymphocytes. The serum did not inhibit the cytotoxic effect of lymphocytes. 7. Mechanism of cyst formation of a glioma was discussed from a view point of immune reaction.
A role of brain in cell-mediated immunity and non-specific immunotherapy for brain tumor patients were studied, not only experimentally but also clinically, employing stereotaxic operation and intravenous injection of heparinoid extracted from tragacanth gum (TGDS). The following interesting results were obtained: 1. Destruction of the striatum in rabbits leads to hypofunction of the reticuloendothelial system (RES) and lymphopenia in the peripheral blood. 2. Unilateral thalamotomy for involantary movement or thalamic pain caused lymphopenia, mainly of T-cell, as well as decrease of IgE globulin in the peripheral blood of the patients. 3. In the tumor bearing host with severe disturbance of consciousness lymphopenia in the peripheral blood or suppressed function of cell-mediated immunity occured frequently. This phenomenon is considered to be the result of dysfunction of brain stem, including basal nuclei. 4. The effectiveness of heparinoid (TGDS) was proved clinically, and tuberculin (PPD) skin test turned positive in patients with marked dysfunction of RES and negative PPD reaction after TGDS administration and transfusion of fresh blood from TGDS administered donors.
Old reported in 1961 that BCG inoculations apparently prevented the establishment of tumor by chemical agent in animals, and Mathe and Morton reported good results using BCG for leukaemia and melanoma patients. The PPD reaction and the number of peripheral lymphocytes of patients with neurosurgical diseases were studied. BCG (0.1-8 mg) was inoculated, from once to several times, intradermally to 68 patients with malignant brain tumors whose PPD reactions were negative. The results were as follows: 1. Most patients with malignant brain tumors showed negative PPD reactions and lymphocytopenia. On the other hand, PPD reactions on patients with benign tumors or without tumor were mostly positive, and lymphocytopenia was rarely noted; 2. In 69.2% of cases, PPD reaction turned to positive after BCG inoculation; 3. The prognosis was compared between the glioma patients with or without BCG inoculation. The 2-year and 3-year survival rates of the former group were 68.40% and 37.5% respectively, which were significantly higher than those of the latter group (2-year survival: 25.0%, 3-year: 12.5%). The average survival time of the former was about 24 months which was about 7 months longer than that of the latter. As for the patients with metastatic brain tumors, the prognosis of the BCG combined group was best, among the 5 groups treated with various combination of therapies; 4. When prognosis were compared between patients whose PPD reaction turned to positive and whose PPD reaction remained negative after the repetitive inoculation of BCG, it revealed that the survival rate was significantly higher in the former. Two cases, one with glioblastoma multiforme and the other with metastatic brain tumor from the uterus, who showed good clinical courses by BCG therapy are also presented. Among the side effects of BCG, fever, local pain and ulceration, and appetite loss were common, but they were transient and easily controlled. No cases of anaphylaxis, or dysfunction of liver and/or kidney were recognized. Though the mechanism of BCG effects to malignant tumors has not yet been well elucidated, following mechanisms are suggestive: 1. It stimulates the reticuloendothelial system to increase the number of macrophages; 2. Its adjuvant action increases the antigenicity of the tumor, and makes the host easier to recognize the tumor specific antigen; 3. It involves non-specifically the tumor cells in the specific inflammatory reaction when introduced into the tumor. It is concluded that the immunosurveillance systems in patients with malignant brain tumors have deteriorated, and the use of BCG as an adjuvant immunotherapy for such cases is recommended.