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Twenty-seven patients with Graves' disease and progressive ophthalmopathy in an advanced stage underwent a transtemporal orbital decompression. The short-term results, i.e. within 2 months, of 48 operations are reported. Prior to the decompression, oral prednisolone, 20–60 mg daily, was given for 2 to 9 months to 15 patients. A minority of patients experienced temporary improvement during steroid administration. Cushing's syndrome was initiated in all patients. Prednisolone little altered the course of the progressive ophthalmopathy. Orbital decompression was followed by increasing visual acuity in 8/22 eyes with disturbed vision, a temporary decrease in 6 eyes, and unaltered visual acuity in the remaining 8 eyes. The decompression removed oedema of the optic disc in all eyes, cured glaucoma in 3 out of 5 patients, caused retraction of the eye bulbs by 5–6 mm in almost all operated cases, and increased compressibility of the orbital content from low (2–5 mm) to normal (6–10 mm) values. Surgery also relieved photophobia and lacrimation, but the effect on diplopia was uncertain. Generally, the decompression was followed by a rapid improvement of the orbital congestion and the patients recovered satisfactorily from the surgery.

Parkinson's disease has been the object of several therapeutic strategies based upon replacement of the degenerating dopaminergic neurons. Adrenal medullary transplants were tried initially, because of the biochemical relationship between chromaffin cells of the medulla and dopaminergic neurons of the substantia nigra. Compared to transplant of fetal neurons, autologous grafts of adrenal medullary tissue has the advantage of using a readily available source of tissue without the problems of immunosuppression. However, these cells have not proven to be as effective as fetal neurons, probably because they do not fully differentiate into neurons. In animal models, brief treatment with nerve growth factor can facilitate such differentiation. This study is a clinical evaluation of the efficacy of adrenal medullary cell transplantation, combined with nerve growth factor infusion. Two patients were selected who were moderately to severely affected (Hoehn-Yahr stage 2 in on-phase and stage 4 in off-phase). After adrenalectomy, small pieces of medulla were prepared and implanted stereotactically into the dorsal putamen on one side of the brain. A catheter filled with mouse beta-nerve growth factor (NGF) was placed close to the grafts. Infusion of NGF was continued for one month. Despite a progressively deteriorating course prior to surgery, both patients showed improvement on the rating scales postoperatively. There was also significant improvement in timed motor tests. Motor readiness evoked potentials showed increased voltage over the operated hemisphere. The study points to methods and feasibility of supplying nerve growth factor intraparenchymally to the human brain. Possible implications with respect to other growth factors, particularly Glial cell-line Derived Neurotrophic factor (GDNF) are discussed.

Fifteen patients were treated in the Gamma Knife Unit and followed for 18 months or longer. Four patients had Cushing's disease, 4 had acromegaly, 3 had Nelson's syndrome and 3 had prolactinomas. One patient had no endocrinopathy. One of the patients with acromegaly and 2 of those with prolactinomas had been operated prior to Gamma Knife treatment. Radiological tumor localization was not an insuperable problem in this series. The effect of Gamma Knife treatment on the anterior pituitary neoplasia, as such, was consistently successful. All the tumors which received 10 Gy or more to the edge showed either a reduction in volume or at least cessation of growth. On the other hand, the effect of the treatment was less consistent in respect to the endocrinopathies. These results are discussed in respect of dose and tumor size. It is suggested that the role of the Gamma Knife in the treatment of pituitary adenomas requires further clarification, based on prospective studies.

The invasiveness of human intracranial tumours was studied in an organ culture system. Biopsies from six glioblastomas, four astrocytomas, two mixed gliomas, one ependymoma, four meningiomas and two carcinoma metastases were cut into fragments of 0.5 mm diameter, and placed in agar overlay tissue culture. The tumour specimens formed spheroids which were co-cultured with cell aggregates or fragments from fetal rat brain for up to 10 days in vitro. The invasiveness of the glioblastoma spheroids was characterised by a gradual destruction of normal brain tissue by tumour cells, followed by replacement of normal tissue by these cells. Co-cultures from two glioblastomas showed lesions in the normal brain tissue in areas removed from the tumour cells. Tumour spheroids from four glioblastomas totally destroyed the normal brain tissue without any change in the original tumour spheroid configuration. The low-grade gliomas were less invasive than the glioblastomas. The meningiomas and the metastases were non-invasive. This organ culture assay appeared to reflect the in situ invasive behaviour of the brain tumours examined. It is suggested that it may be used for evaluating the aggressiveness of individual brain tumours with the specific aim of correlating clinical data with the biological character of the tumour.

In my country, Sweden, the concept of ‘brain death’ was not accepted formally by the law until 1988, after a long and partly heated debate, even an agitated dispute within the medical community itself. Now, after more than 10 years, the debate still has a tendency to flourish occasionally, and, interstingly, opinions thus expressed by the lay public have gradually influenced both the legislative process and the practice, for example the introduction of a voluntary Donor Card system.

In Bergen, 20 patients with meningiomas have been treated with a follow-up period in excess of 1 year. While this is too short a period to allow more than tentative conclusions to be drawn, some trends can be determined nonetheless. There has been some variation in the reporting of the results of treatment of meningiomas, with one group producing a reduction in size in 7% of patients and another in 34%. In the current material, 10 patients received 10 Gy or less to the edge of the tumor. In 4 of these 12 patients there was increase in the volume of the tumor within 1 year of treatment. Ten of the patients received 12 Gy or more to the edge of the tumor. Of these 10 patients, 4 had tumors which showed a reduction in volume. It is suggested that the difference in the reported rate of tumor volume reduction is related to differences in dose, which is discussed in relation to other treatment parameters.

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.

A Leksell Gamma Knife has been used at Haukeland Hospital, Bergen, since October 1988. This is a powerful instrument in the treatment of some intracranial lesions. The article briefly describes the principles of treatment and the uses and limitations of the Gamma Knife.

Four patients with pituitary dependent Cushing's syndrome were treated with external irradiation to the pituitary using 60Co gamma irradiation given with a stereotactic technique. The size of the sella turcica was normal or slightly enlarged in all patients. The doses given varied between 7000 and 10 000 rad, and the observation time ranged between 14 and 20 months. Three of the patients showed complete clinical remission and one marked improvement. One patient developed ACTH insufficiency, while none developed insufficient secretion of other pituitary hormones. No complications of the irradiation were observed.

Fourty-two consecutive patients with craniopharyngioma were treated by "stereotactic approach", i.e. preferentially stereotactic puncture and installation of colloid isotope into cystic tumours and external stereotactic single dose irradiation to solid tumour parts. In a minority of cases, such treatment was less suitable, and surgical removal and/or radiotherapy was used. There was no peroperative mortality. A long-term follow up (observation time 10-23 years) of the 31 patients alive indicated that they were socially well adapted with a high rate of fulltime work and a low rate of intercurrent disease. In spite of substitution therapy for pituitary insufficiency in most cases, the patients were subjectively seldom disturbed by their disease. Our results support a change in the choice of therapy for craniopharyngioma patients, from open neurosurgery to the less invasive stereotactic techniques.

A pituitary tumor secreting TSH only was diagnosed in a 19-year-old male. The patient was clinically euthyroid, but showed elevated TSH, T3 and T4 levels in blood. After selective excision of the tumor it was analyzed with regard to morphology, type of hormone secretion and DNA content. A considerable pleomorphism of pituitary tumor cells occurred. During in vitro culture only TSH was secreted. The tumor had an aneuploid DNA content.

A multi-modality treatment programme, where stereotactic methods were used preferentially, gave results in a consecutive series of craniopharyngiomas, not inferior to those reported after microsurgical removal. Fourty-two patients with a follow-up range of 10-23 years are reported.

The modern adjuncts of improved anaesthesia, endocrine supervision and therapy and also of microsurgery have reduced the risks confined to radical surgery in craniopharyngiomas. Nevertheless, the overall operative mortality reported in recent papers approximates 15%. In addition, many of the survivors are reported as more or less disabled. Against this background the need for improved methods of treatment is obvious. By means of stereotaxis these lesions can be punctured for biopsies, decompression of cysts and intracavitary radionuclide treatment.

In spite of the recent advances in brain surgery, the operative treatment of many intracranial conditions still offers great technical difficulties. The use of the operating microscope, especially in dextrous hands, considerably increases the possibility of achieving gratifying clinical results, but nevertheless the removal of some brain tumours, even benign, is still attended by considerable risks. Furthermore, arteriovenous malformations may if deep-seated be practically inaccessible to conventional techniques. These technical problems, inherent in traditional operations lend a sense of urgency to the development of new therapeutic methods.

The primary aim of this chapter is to familiarize the reader with the diagnostic and, above all, therapeutic implications for a patient with cancer, who presents with symptoms indicating CNS involvement of the malignant disease, often unexpectedly. The current opinion concerning indications for surgery will be described comprehensively, from the author’s personal perspective but also as it is mirrored in relevant reviews from the current neurosurgical literature on metastasis to the brain (Burger and Vogel 1976; Posner and Shapiro 1976; French and Ausman 1977; Whitehouse and Kay 1979; Gamache et al. 1982; Black 1982) and to the spine (Barcena et al. 1984; Murray 1985; Overby and Rothman 1985; Siegal and Siegal 1985; Harrington 1986; Sherman and Waddell 1986; Sundaresan et al. 1986).

On the basis of remarkable results from transplantation experiments in animals, the author in 1979 suggested autologous transplantation of catecholamine tissue to the brain as tentative treatment for parkinsonism. Experiences from four patients thus treated are reported comprehensively. Transitory rewarding effects were seen when the transplant was deposited in the putamen. The potential prospects for this principally new therapeutic paradigm are discussed, as well as possible improvements in the method.

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.

Stereotactic radiosurgery has been used to treat five arteriovenous malformations, in which surgical excision could not be carried out, using the “Co Gamma Unit.

On the basis of remarkable results from transplantation experiments in animals, the author in 1979 suggested autologous transplantation of cathecholamine tissue to the brain as tentative treatment for parkinsonism. Experiences from four patients thus treated are reported comprehensively. Transitory rewarding effects were seen when the transplant was deposited in the putamen. The potential prospects for this principally new therapeutic paradigm are discussed, as well as possible improvements in the method.

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.

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.

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.

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.

Craniopharyngiomas are histologically benign tumors, which can be divided in 3 groups (9): (1) Predominantly, cystic, with a large solitary cyst (about 60% of all cases). (2) Cystic, often polycystic, with an appreciable solid portion (about 30% of all cases). (3) Predominantly solid, no cysts observable. The main pathophysiological factor in the development of clinical symptoms are usually the cysts, whereas the solid, often calcified portions in tumors of group 1 seem to be of less importance. Attempts at radical microsurgical removal of these cysts are often followed by severe hypothalamic disorders, recurrences are frequent. Evacuation of the cyst by puncture is usually followed by rapid refilling. Conventional radiotherapy has been found to be more effective than previously assumed. High-dose irradiation may cause complete destruction of the tumor, but persistent hypothalamic and optic disorders are to be encountered (7).

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.

As human malignant gliomas of the brain cannot be treated successfully by conventional means, i.e., bulk resection + radiotherapy, eventually combined with the systemic administration of cytostatic agents, we decided to start a trial consisting of stereotactic biopsy of the tumour and placement of a small catheter in the center of the tumour to administer chemotherapeutic agents. In contrast with those agents used in systemic administration that should be of small molecular size and lipid soluble to penetrate the CNS, for intraneoplastic drug delivery drugs could be used that do not pass the blood brain barrier. It seemed reasonable to chose a drug that will neither pass this barrier nor the brain-blood barrier. Besides that the drug should be a non-cell cycle specific drug as gliomas have a very low growth fraction 5 and should have shown at least some effectivity against glioma cells both in vivo and in vitro 7-9. Bleomycin fulfilled all these criteria 2, 6 and has been taken as the first agent to test in this way.

Irradiation of the basilar artery of cats by stereotactic technique was performed with doses varying from 100 to 300 Gy in a gamma unit. Histologically, vascular lesions such as vacuolization, degeneration and desquamation of the endothelium and hyalinization and necrosis of the muscular coat predominated, whereas reparatory reactions were relatively sparse. Thrombosis was completely absent.

(1972). Closed Stereotaxic Hypophysectomy by Means of 60Co Gamma Radiation. Acta Radiologica: Therapy, Physics, Biology: Vol. 11, No. 6, pp. 545-555.