A computer-assisted neurosurgical navigational system has been developed which displays intraoperative manipulation on the preoperative computerized tomography (CT) scans or magnetic resonance (MR) images. The system consists of a three-dimensional digitizer, a personal computer, and an image-processing unit. Utilizing recently developed magnetic field modulation technology, the three-dimensional digitizer determines the spatial position and orientation angles of the resin probe, triangle-shaped pointer, or suction tube with a small attached magnetic field sensor. Four fiducial markers on the scalp were used to translate the spatial data of the probe onto the preoperative CT scans or MR images of the patient. With this frameless, armless navigational system, CT or MR-imaging stereotaxy can be applied to conventional open neurosurgery without limiting the operative field or interfering with the surgical procedures.
We studied functional disturbances following left middle cerebral artery occlusion in rats. Neuronal function was evaluated by [ 14 C]2-deoxyglucose autoradiography 1 day after occlusion. We analyzed the mechanisms of change in glucose utilization outside the infarct using Fink-Heimer silver impregnation, axonal transport of wheat germ agglutinin-conjugatedhorseradish peroxidase, and succinate dehydrogenase histochemistry. One day after occlusion, glucose utilization was remarkably reduced in the areas surrounding the infarct. There were many silver grains indicating degeneration of the synaptic terminals in the cortical areas surrounding the infarct and the ipsilateral cingulate cortex. Moreover, in the left thalamus where the left middle cerebral artery supplied no blood, glucose utilization significantly decreased compared with sham-operated rats. In the left thalamus, massive silver staining of degenerated synaptic terminals and decreases in succinate dehydrogenase activity were observed 4 and 5 days after occlusion. The absence of succinate dehydrogenase staining may reflect early changes in retrograde degeneration of thalamic neurons after ischemic injury of the thalamocortical pathway. Terminal degeneration even affected areas remote from the infarct: there were silver grains in the contralateral hemisphere transcallosally connected to the infarct and in the ipsilateral substantia nigra. Axonal transport study showed disruption of the corticospinal tract by subcortical ischemia; the transcallosal pathways in the cortex surrounding the infarct were preserved. The relation between neural function and the neuronal network in the area surrounding the focal cerebral infarct is discussed with regard to ischemic penumbra and diaschisis. {Stroke 1989;20:1226-1235) T he neuronal network, consisting of neurons and fibers, maintains the neuronal functions in the central nervous system. Therefore, even though an injury to the central nervous system is limited to a focal region, it may affect the blood flow, metabolism, and function of other brain regions. This pathophysiology has been named diaschisis.1 Recent advances in positron emission tomography (PET) may help to elucidate this phenomenon. In stroke patients, occlusion of a major intracranial artery results in ischemia of not only the cortical gray matter but also of subcortical structures. For example, PET clearly showed that a subcortical ischemic lesion and thalamic stroke affected the cerebral blood flow and glucose utiliza-
A randomized clinical study of irradiation and irradiation combined with ACNU in the treatment of malignant gliomas was performed in order to determine if there was an enhancing therapeutic effect of ACNU given in addition to radiotherapy. An effect was defined as a reduction in tumor size, changes in neurological signs and performance status within 1 month after the completion of radiotherapy, or statistically improved survival times. Seventy-seven patients from 14 neurosurgical clinics were included in this validated study group. Radiotherapy with a total dose of 5000 to 6000 rads, given in 25 to 30 subdoses, was applied to the whole brain and to a generous field surrounding the tumor. Patients who were assigned to receive chemotherapy were given ACNU intravenously once or twice during radiotherapy at a dose of 100 mg/sq m of body surface area. The response rate (more than 50% reduction of the tumor size) was 13.5% in the group treated by radiotherapy alone and 47.5% in the group with radiotherapy and ACNU. The hematological toxicity was more severe in the group treated with radiotherapy and ACNU. Other toxicity was mild and acceptable. The survival rates of patients with astrocytoma grade III and glioblastoma multiforme at 36 months after the surgery were 48.9% and 0% for radiotherapy alone and 59.0% and 16.3% for radiotherapy plus ACNU, respectively. The differences between the survival curves were not significant at the p = 0.05 level. This study has demonstrated that, although the use of ACNU during radiotherapy suppressed malignant gliomas more than radiotherapy alone, the survival time was not extended significantly. It is necessary to continue to search for an effective chemotherapeutic regimen to prolong survival of patients with malignant gliomas.
An experimental model for blood-borne cerebral metastases was developed by introducing Walker 256 carcinoma cells selectively into the intracranial internal carotid artery of rats. This model was used to study the regional capillary permeability of rat brain and metastatic brain tumors of various sizes with the aid of 14C alpha-aminoisobutyric acid (AIB) quantitative autoradiography. The regional capillary permeability varied with the anatomical location and size of the tumor. Intraparenchymal tumors less than 1 mm in diameter showed no increased permeability to AIB. As the tumors enlarged over 1 mm in diameter, the permeability in the intraparenchymal tumors increased proportionally, but remained less than one-third of capillary permeability of subcutaneously transplanted tumors. Capillary permeability in the peripheral invasive part and necrotic center was less than in the viable part of large tumors. Capillary permeability in metastatic tumors of the choroid plexus and meninges was significantly higher than in tumors of the brain parenchyma. The results suggest that the uptake of chemotherapeutic agents that do not cross the blood-brain barrier easily varies with the anatomical location and size of the metastatic tumors.
A controlled randomized study was carried out to evaluate the effects of chemotherapy in patients with brain metastases from lung carcinoma. One hundred patients were randomly divided into three groups at the time of diagnosis or after surgery for metastases. Group A received radiotherapy alone; Group B received radiotherapy and chloroethylnitrosoureas (methyl-CCNU, 100-120 mg/m2, or ACNU 80-100 mg/m2, every 6-8 weeks), and Group C received radiotherapy and a combination of chloroethylnitrosoureas and tegafur (300 mg/m2. daily). Of the 100 patients, 88 could be evaluated. The reduction rates of the tumors of the patients in whom tumor was not surgically removed or not totally removed were compared. Complete resolution of the tumor was noted in 29, 69, and 63% of the patients in Groups A, B, and C, respectively, Tumor regression of ⩾50% was seen in 36, 69. and 74% of the patients in Groups A, B, and C, respectively. The difference in the response rates of Groups A and C was statistically signficiant (P<0.05). Median survival after the start of treatment for brain metastasis was 27, 30.5, and 29 weeks in Groups A, B, and C, respectively. There was 1 long-term survivor (more than 5 years) in Group A, 3 in Group B, and 1 in Group C. The main cause of death was deterioration attributable to the primary lesion or systemic metastasis, and no statistical difference was noted in survival time among the groups. Our results indicate that combination chemotherapy with chloroethylnitrosoureas and tegafur has an additive effect on radiotherapy in reducing or eliminating brain metastases from lung carcinoma, and that brain metastasis is well controlled by multidisciplinary treatment including chemotherapy.
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