Leptomeningeal tissue: a barrier against brain tumor cell invasion.

BACKGROUND: Primary brain tumors are characterized by an extensive infiltrative growth into the surrounding brain tissue. This process is confined to the central nervous system, and tumor cell metastasis to other organs is rare. However, other tumors of non-neural origin may frequently metastasize to the central nervous system. PURPOSE: The purpose of the present study was to examine the invasive behavior of different glioma cells into tissues of neural (brain aggregates) as well as non-neural origin (leptomeningeal tissue). Using the same target tissues, the invasive characteristics of two neural metastatic tumors (one malignant melanoma and one small-cell lung carcinoma) were also studied. This direct comparison of the invasive behavior between tumors of neural and non-neural origin provides valuable information regarding the mechanisms of glioma cell dissemination in the central nervous system. METHODS: The in vitro invasive behavior of human tumors of the central nervous system into human leptomeningeal tissue as well as into normal rat brain tissue was studied. For this purpose, a co-culture system consisting of tumor biopsy specimens, human leptomeningeal cell aggregates, and brain cell aggregates was established. Three glioblastomas, one oligodendroglioma, one meningioma, one small-cell lung carcinoma, and one malignant melanoma were studied. RESULTS: In co-cultures of gliomas and leptomeningeal cell aggregates, a well-defined border between the two tissues was observed. The brain cell aggregates, in contrast, were consistently invaded by the glioma cells. The brain metastases showed a different invasion pattern. The metastatic cells invaded and progressively destroyed leptomeningeal cell aggregates, whereas they did not invade the brain cell aggregates. Upon confrontation of the leptomeningeal tissue with the meningioma, a fusion of the two tissues was observed. Immunostaining of the leptomeningeal tissue showed a strong expression of the basement membrane components fibronectin, collagen type IV, and laminin with no expression of glial fibrillary acidic protein, neuron-specific enolase, or S-100 protein. CONCLUSIONS: The present study indicates that there may be important biologic differences between the invasive behavior of gliomas and non-neuroepithelial tumors. Our co-culture experiments suggest that leptomeningeal cells and associated acellular components may constitute a barrier against glioma cell invasion. However, this barrier may not be functional for metastatic tumors to the brain. The presence of glioma cells within the leptomeninges should not necessarily be taken as evidence of aggressive growth or as an indicator of malignancy.

Intraputaminal infusion of nerve growth factor to support adrenal medullary autografts in Parkinson's disease. One-year follow-up of first clinical trial.

Experimental studies in rodents show that beta-nerve growth factor can increase the survival, neurite outgrowth, and functional effect of grafts of adrenal chromaffin cells to the basal ganglia. We, therefore, have begun to investigate whether treatment with nerve growth factor might also increase the functional effect of autografts of adrenal medullary tissue in patients with Parkinson's disease. Previous studies have shown that stereotactic implantation of adrenal tissue pieces produces a transient functional improvement that lasts for a few months. This report describes a trial of grafting of adrenal chromaffin tissue into the putamen, supported by infusion of nerve growth factor. The patient is a 63-year-old woman with a 19-year history of Parkinson's disease, now complicated by on-off phenomena and drug-induced hyperkinesia, despite optimized medical management. The left adrenal gland was removed, and the medulla was dissected into 1- to 2-mm3 pieces in a solution containing nerve growth factor purified from mouse submandibular gland. Pieces were implanted in six tracts 3 to 4 mm from a previously placed cannula in the left putamen. Through the cannula, nerve growth factor was infused for 23 days for a total dose of 3.3 mg. Clinical assessment consisted of global ratings for rigidity and/or hypokinesia and for drug-induced hyperkinesia. Measures of gait and fine-motor control were also made. The motor readiness potential and auditory evoked potentials were recorded.(ABSTRACT TRUNCATED AT 250 WORDS)

Stereotaxic reconstruction of the aqueduct of Sylvius.

A stereotaxic technique has been developed to cannulate the cerebral aqueduct in patients with hydrocephalus resulting from occlusion of the aqueduct of Sylvius. Precise placement of a 15- to 20-mm long radiopaque prosthesis between the third and fourth ventricles can reestablish the normal cerebrospinal fluid (CSF) pathway. Since 1974, seven patients have undergone aqueductal reconstruction. The surgical goal in this series was to manage the hydrocephalus by creating and maintaining a patent aqueductal channel. The follow-up period ranged from 1.5 to 6.5 years. In four cases, aqueductal reconstruction alone resulted in control of the hydrocephalus, although two patients underwent revisions of their prosthesis. Three patients ultimately required shunts, despite initial symptomatic improvement after reconstruction. In these seven cases (13 stereotaxic procedures), no mortality and no significant operative morbidity were encountered. Although the technique is relatively simple to perform, technical difficulties remain. At present, no clinical or radiographic test adequately discerns the ideal candidate for stereotaxic aqueductal reconstruction. Four patients required stereotaxic revision because of malposition or malfunction of the prosthesis. This approach should be reserved for patients with a short aqueductal occlusion, and normal distal CSF pathways and dynamics. The rationale, technique, problems, and results of stereotaxic reconstruction are presented.

Multicellular tumor spheroids from human gliomas maintained in organ culture.

Tumor tissue from seven human gliomas was maintained in long-term agar overlay culture as multicellular organotypic spheroids. Light microscopic and ultrastructural observation of the spheroids displayed morphological features similar to those of the original tumor tissue in vivo; in this respect they were different from spheroids obtained from permanent cell lines. The spheroids contained preserved vessels, connective tissue, and macrophages, revealing a close resemblance to the conditions in the original tumor. Flow cytometric deoxyribonucleic acid measurements of cells from the tumor spheroids and from biopsy material obtained directly from the operation revealed the same ploidy and the same amount of proliferating cells in the spheroids as in the original tumor. Fluorescence microscopy using bromodeoxyuridine (BUdR) incorporation and anti-BUdR monoclonal antibody confirmed the proliferative potential of tumor cells in the spheroids. Diameter measurements showed that the size of the spheroids from two of the tumors increased over time while in three other cases it decreased. Spheroids from the remaining two tumors showed no change in size, even after 80 days in culture. These growth data and the relatively high number of proliferating cells, as measured by flow cytometry, indicate that the degree of cell proliferation and cell loss from the spheroids are closely linked, as is the case for tumors in vivo. The culture system presented provides a valuable alternative to propagation of human tumors in animals.

Transplantation of adrenal medullary tissue to striatum in parkinsonism. First clinical trials.

Autologous adrenal medullary tissue was transplanted to the striatum in two patients with severe parkinsonism. The aim was to provide the striatum with a new cellular source of catecholamines. Some rewarding effects were registered. This is the first time that such tissue has been transplanted in the human brain. The results merit further clinical trials.

Effects of high and low single dose irradiation on glioma spheroid invasion into normal rat brain tissue in vitro.

The effects of radiation on direction on directional migration in monolayer cultures and brain tissue invasion by two glioblastoma cell lines (D-54 MG, D-247 MG) were investigated. The Leksell Gamma Unit was the radiation source and invasion was registered in an in vitro invasion assay developed in our laboratory. As tumor spheroids and brain tissue aggregates were treated simultaneously in cocultures; the effects of radiation on the interaction between the two tissues could be investigated. Tumor spheroids from both cell lines retained their ability to invade and destroy normal brain tissue, even after irradiation with 47.6 Gy. However, while the D-54 MG tumor spheroids showed a dose-dependent reduction of invasion, tumor spheroids from the D-247 MG cell line did not. In addition, radiation produced a dose dependent inhibition of directional migration of cells from D-54 MG spheroids. A similar significant inhibition of directional migration was found in D-247 MG, but it was not dose-dependent. Transmission electron microscopy revealed a loosening of the neuropil in the brain tissue of irradiated cocultures. However, this structural change did not seem to affect the invasiveness of the tumor. In this preliminary study, irradiation could not prevent invasion of two different glioblastoma cell lines into fetal rat brain tissue. Further studies using the same technique may help to understand the influence of ionizing radiation upon the invasion process in gliomas.

Stereotactic catheter insertion: a new technique.

In spite of modern instrumentation that is widely available, inaccurate and even crude techniques are still occasionally used for puncturing cavities within the cranial cavity. Thus, a standardized technique for intracranial puncturing, based on stereotaxy, is suggested and illustrated by some clinical cases.

Radiosurgery in intracranial tumors and vascular malformations.

In 1951 Leksell first coined the term "radiosurgery" indicating a new tool for the neurosurgeon by means of ionizing radiations. The technique consists of cross-firing a stereotactic target with several well-collimated "shots" of radiation. This produces well-defined lesions in the brain without opening the skull. After several significant improvements of this technique, now assisted by a computer, today it is possible to "tailormake" composite radiation fields for any single lesion. Some interesting clinical applications are Cushing's disease, acoustic tumors, pineal region tumors and arteriovenous malformations.

Colloidal radioisotopes as part of a multi-modality treatment of craniopharyngiomas.

The therapy of craniopharyngiomas has always been a challenge for the neurosurgeon. These tumors often display a cystic or polycystic portion usually bigger than the solid portion. This paper reports therapeutic results in a series of 42 cases; the follow-up range is 10 to 23 yrs. The results are particularly rewarding in the group treated by stereotactic methods exclusively. In any case the optimal management of a craniopharyngioma should include a careful study of the anatomy of the tumor and the intracystic treatment as the first choice if more than 50% of the total tumor bulk is cystic and the number of cysts reasonable.

Stereotactic biopsies as a model for studying the interaction between gliomas and normal brain tissue in vitro.

In order to study tumor invasiveness, the authors used a model system which allows the direct interaction between glioma cells and normal brain tissue to be studied. The spiral needle biopsy technique provides a tissue core with a completely preserved architecture from brain tumors. These biopsies, once cultured, produce three-dimensional multicellular tumor spheroids; they display morphological features similar to those of the original tumor in vivo. As a target fetal rat brain cell aggregates were used, in order to study the invasive process in the microscope. Not surprisingly, different tumors show different patterns of invasion; this variability is not yet clearly correlated with the clinical course of the patient.

Controlled subtotal evacuation of intracerebral haematomas by stereotactic technique.

A new instrument for stereotactic evacuation of intracerebral haematomas is presented, as well as preliminary clinical experiences. A combined screw-and-suction technique makes possible the evacuation of even densely coagulated clots. The principle for a limited removal of a hemorrhagic mass in the brain is discussed.

Treatment of colloid cysts of the third ventricle by stereotactic aspiration.

Four patients are described with a colloid cyst in the anterior part of the third ventricle, causing obstruction of the foramina of Monro. Stereotactic aspiration of the cyst was performed after exact neuroradiological localization, including CT scan. The great advantages of the technique presented are discussed.

Stereotactic radiosurgery in Cushing's syndrome: acute radiation effects.

Stereotactic radiosurgery was used for selective destruction of adrenocorticotropic hormone (ACTH)-producing adenomas in 18 patients with Cushing's syndrome. A radiation-induced lesion in the most anterior part of the sella turcica caused remission of the disease. The acute increase in ACTH and cortisol secretion that occurred in the majority of patients had no predictable relationship to the final outcome. Decreased cortisol excretion during the first three weeks after treatment was positively correlated to favourable long-term results. The treatment is a therapeutic alternative to open selective excision of the adenoma.

Transcerebellar biopsy in the posterior fossa: 12 years experience.

Utilizing the Leksell stereotactic system, the transcerebellar approach was used for posterior fossa biopsies. During a period of 12 years, a total of 29 patients were operated on by this technique, among them 12 children. In the adult, the procedure was carried out with the patient awake and sitting upright; the pediatric patients required general anesthesia and the head was supported either manually or by a clamp. Representative specimens were obtained in all cases but one, showing a wide diagnostic spectrum. As a rule, the procedures were performed smoothly, with no serious side effects. Stereotactic biopsies in the posterior fossa, hitherto seldom performed, open new diagnostic perspectives, one of which is for use in obscure brain stem lesions. The transcerebellar approach has been proven to be easy, direct, and safe provided an appropriate technique is used, such as that described in the present paper.