Postoperative radiotherapy of medulloblastoma. Impact of radiation quality on treatment outcome.

Between 1975 and 1991, 40 patients with newly diagnosed medulloblastoma of the posterior fossa were treated at the authors' institutions. After aggressive surgical resection 39/40 patients (98%) received craniospinal radiation therapy (RT), including a local boost. A group of 29 patients was treated with adjuvant chemotherapy. The estimated overall 5-year survival and 5-year relapse-free survival (RFS) probabilities were 75% and 65%, respectively. The 5-year survival was significantly prolonged for patients treated after 1981 as compared to those treated between 1975 and 1980 (80% vs 64%, p = .02). However, multivariate analysis identified the adequate coverage of the target volume by external RT as the only significant variable (p = .0031). The extent of resection, stage according to Chang, radiation dose to the posterior fossa (< 55 Gy vs > or = 55 Gy) and the use of chemotherapy did not significantly influence survival and RFS. The initial site of recurrence was the posterior fossa with or without disseminated central nervous system (CNS) disease in 5 patients, the CNS without posterior fossa in 4 patients, and the bone marrow in 2 patients. An isolated frontal relapse occurred in 1 patient. We conclude that quality control of RT plays a decisive role in the long-term outcome of patients with medulloblastoma.

Proliferation parameters for pituitary adenomas.

In this review, the value of assessing proliferation parameters in surgically resected pituitary tumour tissue is analyzed. Histological examination of basal dura biopsies identifies invasive growth even when intraoperatively not apparent to the surgeon. Determination of DNA-polymerase activity, Ki-67 immunohistochemistry and DNA-flow-cytometry shows a clear difference in the proliferative potential of enclosed and invasive pituitary adenomas. Among the various endocrinologically differentiated groups ACTH-secreting adenomas associated with Nelson's syndrome and thyrotropinomas were the most rapidly proliferating. At present, however, our results reveal that the prognosis of an individual patient cannot be reliably predicted on the basis of such studies.

A case of Alzheimer's disease with extensive focal white matter changes.

The case of a patient is reported who suffered from disturbed concentration and memory and constructive apraxia. She had only mild neuropsychological deficits at the first examination. T2-weighted MRI presented extensive focal white matter changes. A brain biopsy showed changes typical for Alzheimer's disease (AD). The extent of the white matter lesions was surprising compared to the mild clinical signs she had. This case confirms that AD may result in prominent white matter disease caused by incomplete infarction or demyelination.

Human chorionic gonadotrophin immunoactivity in cystic intracranial tumours.

BACKGROUND AND OBJECTIVE: With regard to intracranial tumours, elevated hCG in CSF or serum has been considered to be specific for germ-cell tumours. Recently however, elevated hCG has also been shown to be present in cyst fluid and CSF of patients with craniopharyngiomas. While germ-cell tumours are generally non-cystic, the aim of our study was to determine the significance of hCG in cystic intracranial lesions. DESIGN: In a prospective study, hCG immunoactivity and subunits of hCG were measured in cyst fluid, CSF, and serum of patients harbouring intracranial cyst lesions. PATIENTS AND MEASUREMENTS: hCG immunoactivity was measured in cyst fluid and serum samples of 42 patients. CSF samples were available from 12 patients with craniopharyngiomas. In order to fully characterize the hCG immunoactivity, we used immunoradiometric assays for total hCG activity (measuring both intact hCG and the free beta-subunit of hCG), and those specific for intact, dimeric hCG (hCG), free beta-subunit of hCG (hCG beta) and free alpha-subunit. Furthermore, immunostaining of tumour tissue was performed using monoclonal antibodies directed against the free beta-subunit of hCG. RESULTS: Total hCG immunoactivity was markedly elevated in cyst fluid of all 17 craniopharyngiomas (range 36.7-4558 IU/I; normal < 5 IU/I). Moderately elevated levels of hCG in cyst fluid were detected in three of four pituitary adenomas, in two metastases from lung cancer and in two arachnoid cysts. hCG beta was detected in cyst fluid from all hCG positive cysts, while specific determination of intact (dimer) hCG and alpha-subunit mostly yielded negative results. No hCG immunoactivity was found in cystic gliomas, meningiomas or haemangioblastomas. hCG was elevated in CSF of two patients with craniopharyngiomas, but no hCG immunoactivity was detected in any serum sample. Subtle immunostaining of epithelial cell groups was shown in five of ten craniopharyngiomas. Clear immunostaining for hCG beta was also found in scattered epithelial cells of one pituitary adenoma. CONCLUSIONS: hCG immunoactivity in cystic intracranial lesions is due mainly to hCG beta. Measurement of hCG immunoactivity in cyst fluid can be helpful in the differential diagnosis of intracranial cystic lesions, if surgery is restricted to cyst decompression and no histology is available. High levels suggest a craniopharyngioma.

Neuronal protection by intraischemic brain perfusion: an electron microscopy study in the rat.

Organ perfusion with bloodless solutions is an established clinical method for protecting the heart against ischemic damage. In our study, we evaluated the effects of intraischemic bloodless brain perfusion on postischemic ultrastructural neuronal changes in a model of severe incomplete forebrain ischemia produced by hemorrhagic hypotension combined with temporary carotid occlusion in the rat. Four groups of rats were compared. During an ischemic insult of 30 min, the brains of two groups were perfused via both external carotids with either a normosmolar normothermic magnesium-enriched perfusate (MgSO4, 30 mM; NaCl, 37 mM; mannitol, 180 mM; n = 10) or a normothermic normal saline solution (n = 9) at a rate of 6 ml/h. Two other groups (ischemia without perfusion, n = 8; no ischemia and no perfusion, n = 7) served as controls. After 30 min of ischemia, withdrawn blood for hemorrhagic hypotension was reinfused, the carotid arteries reopened, and the brains reperfused for 2 h. After perfusion-fixation, qualitative and quantitative evaluation of postischemic cell changes of hippocampal CA1 neurons was performed by electron microscopy. Brain perfusion with the magnesium-containing solution significantly protected neurons against ischemic cell changes and provided an ultrastructural pattern similar to that seen in the nonischemic control group. In contrast, brain perfusion with normal saline solution did not result in neuronal protection. We conclude that intraischemic intracarotid brain perfusion with magnesium-enriched perfusate protects hippocampal neurons significantly against ischemic cell changes in the early reperfusion period after transient severe forebrain ischemia.

[Thyrotropin-producing hypophyseal adenoma in a case with congenital thyroid gland hypoplasia]. / Thyreotropinproduzierende Hypophysenadenome in einem Fall mit kongenitaler Schilddrüsenhypoplasie.

A 56 year old mentally disabled woman of short stature was admitted to our hospital because of severe chest pain and dyspnoea. An extended myocardial infarction in the anterior wall was clinically found and confirmed by autopsy. On admission cretinism with massive myxedema was diagnosed, which was confirmed by subsequent laboratory findings. Only at the base of the tongue thyroid tissue 3 mm in diameter was found. In the anterior lobe of the pituitary gland areas with nodular hyperplasia and microadenomas of TSH-producing cells were detected. Thyrotroph adenomas in long standing hypothyroidism are rare. There are only few reports on congenital hypothyroidism as primary underlying disease.

Magnetic source localization and morphological changes in temporal lobe epilepsy: comparison of MEG/EEG, ECoG and volumetric MRI in presurgical evaluation of operated patients.

Is MEG source analysis able to precisely locate the primary focal epileptic activity? 22 patients with pharmacoresistant temporal lobe epilepsy were recorded during presurgical evaluation simultaneously with multichannel MEG/EEG and invasive (subdural) electrodes to evaluate the increase of information gained by MEG concerning the localization of focal epileptic activity and lesions. With this systematic study it should become clearer how often MEG can establish a diagnostic bridge between function and morphology. In addition, MEG localization accuracy of focal epileptic activity was to be validated empirically by invasive EEG recordings and postsurgical outcome. Spikes in the MEG were used for magnetic source localization, and the result was combined with magnetic resonance imaging (MRI). All patients definitely suffered from temporal lobe epilepsy and revealed a structural abnormality in MRI. 17 patients with lesions in the temporal lobe were operated meanwhile and became markedly improved or seizure free. In 7 of 8 patients with a tumor and validated operation outcome, a very close correlation of the 3D-magnetic source localization and the border of the tumor in the brain was found (distance less than 10 mm). In 8 of 9 patients with a temporal/hippocampal atrophy and validated operation outcome, dipoles of epileptiform activity were located within the atrophic lobe.(ABSTRACT TRUNCATED AT 250 WORDS)

[Tumor in tumore: breast cancer metastasis in a meningioma]. / Tumor in tumore: Mammakarzinommetastase in einem Meningiom.

A 60-year-old woman had undergone surgery for ductal breast carcinoma. Six years after operation there was no local recurrence, but metastases were found in the liver, lungs and in a meningioma.

[Medulloblastomas--the results after postoperative radiotherapy with and without adjuvant chemotherapy]. / Medulloblastome--Ergebnisse nach postoperativer Radiotherapie mit und ohne adjuvante Chemotherapie.

Between 1975 and 1991, 40 patients with newly diagnosed medulloblastoma were treated at the authors' institutions. After aggressive surgical resection 39/40 (98%) received craniospinal radiation therapy with a local boost to the posterior fossa and other macroscopically involved areas. A group of 29 patients was treated with adjuvant chemotherapy. The five-year actuarial survival and event-free survival were 75% and 65%, respectively. Survival was significantly better for patients treated after 1981 as compared to those treated between 1975 and 1980 (p = .02). Younger age (two to four years) was associated with a better prognosis (p = .02). The extend of resection, Chang-stage, radiation dose to posterior fossa and the use of chemotherapy did not significantly impact on survival and relapse-free survival.

Immunohistochemical expression of protein kinase C type III in human pituitary adenomas.

Immunohistochemical expression of the three major isozymes of protein kinase C--Types I, II, and III--was studied in 32 cases of human pituitary adenomas, and the results were compared in detail with their clinical data. Immunoreactivity for the Type I and Type II isozymes was negative in tumor cells of all pituitary adenomas. Moderate to strong cytoplasmic immunoreactivity for the Type III isozyme was constantly seen in acromegaly, Cushing's disease, and nonfunctioning adenomas, which indicated overexpression of the isozyme, since only slight cytoplasmic immunoreactivity was observed in the normal human anterior pituitary cells. Among 13 prolactinomas, 5 cases showed positive immunoreactivity for Type III in all tumor cells, whereas 8 cases showed negative immunoreactivity for the isozyme in all or more than 85% of tumor cells. The sizes of the tumors in this protein kinase C Type III negative group of prolactinomas tended to be smaller than those of the Type III positive prolactinomas. Also, the negative immunoreactivity for Type III was predominantly observed in those cases where prolactinomas were relatively well controlled by continuous oral dosage of dopamine agonists before operation. These results suggest that protein kinase C Type III is closely involved in human pituitary adenomas. The exceptional negativity for the isozyme in prolactinomas may be relevant to the suppression of tumor growth by dopamine agonists.

The role of transsphenoidal microsurgery in the management of sellar and parasellar meningioma.

We report on eight meningiomas that have been operated on via the transsphenoidal route since May 1988. Six patients harbored cavernous sinus meningiomas with intrasellar extension. The intrasellar tumor extension and the parasellar tumor portion medial to the carotid artery were removed. Decompression of the pituitary gland with normalization of prolactin levels was achieved in all patients. It is a well-tolerated approach to confirm the diagnosis and still allows the option of major transcranial surgery in the event of tumor progression. Additionally, we report complete tumor removal in two rare cases with intrasellar and suprasellar merely subdiaphragmatic meningiomas.

[Prognostic factors and results after the combined surgical and radiotherapy treatment of ependymomas]. / Prognostische Faktoren und Ergebnisse nach kombiniert operativer und strahlentherapeutischer Behandlung des Ependymoms.

Between 1978 and 1991, 31 patients with primary (n = 28) and recurrent (n = 3) ependymoma received external radiation after initial surgery. There were 26 cases of intracranial and five cases of spinal ependymoma. Histological grading revealed low-grade in 23 and high-grade tumors in eight patients. Craniospinal irradiation was given to 13 of 28 patients, whole cranial radiation with boost to posterior fossa in three and local treatment to twelve patients. Six of 28 patients received chemotherapy. Dose to the primary, tumor localisation, grading and extend of surgery did not significantly impact on survival and relapse-free survival. Age was a marginally significant prognostic factor for survival. In patients with intracranial ependymoma (n = 24) survival and relapse-free survival at five years were 54% and 42%, respectively. Patterns of recurrence showed a local recurrence alone in eight, a CNS-relapse with local recurrence in four and local recurrence with distant metastases in one case. Spinal seeding occurred in two of 13 after craniospinal irradiation and two of twelve patients after local treatment. The main problem in the treatment of ependymoma remains local control, the use of spinal irradiation does not seem to improve treatment results.

Autocrine control of human meningioma proliferation: secretion of platelet-derived growth-factor-like molecules.

We have used cell-culture techniques to investigate growth-factor production by human meningioma cells. Meningioma tissue was dispersed with collagenase and the cells grown to high density in tissue-culture flasks. The cultures were used to generate conditioned medium (MEN-CM), which was used to cultivate IMR32 cells (a human neuroblastoma line) and freshly dispersed primary meningioma cells. MEN-CM profoundly stimulated the in vitro growth of both IMR32 and meningioma cells. In addition, H3-thymidine uptake by cultured meningioma cells was increased in a dose-dependent manner by varying concentrations of MEN-CM. A neutralizing anti-body against platelet-derived growth factor (PDGF) completely abolished the stimulatory effects of MEN-CM, whereas an antibody against TGF-alpha was without effect. The mitogenic activity of MEN-CM, as assayed by promotion of H3-thymidine uptake by cultured meningioma cells, eluted from a Sephadex G-100 column in 3 peaks corresponding to molecular weights of greater than or equal to 150, 56 and 28 kDa. Our results show that proliferation of human meningiomas may be under autocrine control via secretion of PDGF-like molecules.

Observations on the pathophysiology of Nelson's syndrome: a report of three cases.

Nelson's syndrome is generally regarded as an unusual sequela of primary bilateral adrenalectomy when performed for Cushing's disease. It is classically defined by cutaneous hyperpigmentation, considerably elevated adrenocorticotropic hormone (ACTH) levels, and an enlarged sella turcica. In this report, we present three cases initially treated by transsphenoidal sellar exploration for Cushing's disease. In two of these cases, remission of hypercortisolism did not occur after the initial pituitary exploration. A microadenomectomy was performed in one case and, in the other, no microadenoma was found. In both, Nelson's syndrome occurred after adrenalectomy. A second transsphenoidal operation and radiotherapy were required to control tumor growth. In another case, transsphenoidal adenomectomy of an ACTH-secreting tumor initially led to a remission of hypercortisolism for 4 years, but recurrent Cushing's disease necessitated adrenalectomy, and again Nelson's syndrome occurred. The documentation of a pre-existing ACTH-secreting basophilic pituitary microadenoma before adrenalectomy, as seen in two of our cases, has not been previously reported, and these observations of "non-classical" courses have major implications for the pathophysiology of Nelson's syndrome.

Wernicke's encephalopathy in two patients with acquired immunodeficiency syndrome.

Two non-alcoholic homosexual patients with acquired immunodeficiency syndrome (AIDS) are reported who developed acute Wernicke's encephalopathy in the terminal stage of their illness. The first patient presented with vascular congestion, minute haemorrhages, proliferation of microglia and of the vessel walls at the predilection sites of the Wernicke-Korsakoff process. In the second patient only the mamillary bodies were involved. Besides Wernicke's encephalopathy, a primary cerebral immunoblastoma and cerebral toxoplasmosis were found in the first patient, whereas the second showed severe encephalitis with numerous microglial and multinucleated giant cells reacting positively with anti-HIV antibody. Just as in the development of Wernicke's encephalopathy in malignant diseases, the catabolic trend of the metabolism of the immunodeficient patients with consecutive thiamine deficiency must be considered the principal pathogenetic mechanism.

Hormonal dependency of cerebral meningiomas. Part 2: In vitro effect of steroids, bromocriptine, and epidermal growth factor on growth of meningiomas.

Cell culture and biochemical techniques have been employed to examine the effects of steroids, bromocriptine, and epidermal growth factor (EGF) on the growth and proliferative potential of meningiomas. In cell culture, the growth of meningiomas was not altered by progestogens, antiprogestogens, or 17beta-estradiol. The progestogen, norethisterone, had no effect on the uptake by meningiomas cell cultures of 3H-thymidine. Furthermore, cytosolic deoxyribonucleic acid (DNA) polymerase activity of meningiomas did not correlate with the progesterone receptor status of the same tumors. In contrast, the androgen antagonists, cyproterone acetate and 11-alpha-hydroxyprogesterone, and the dopamine agonist, bromocriptine, all inhibited the in vitro growth of meningioma cells. The growth of meningioma cell cultures was stimulated by EGF, and there was a positive correlation between the EGF content and DNA polymerase activity in meningioma cytosols. These results demonstrate that female sex steroids do not influence growth of meningiomas in vitro, whereas antiandrogens and bromocriptine have an antiproliferative effect. Consequently, bromocriptine and antiandrogens may have a role in the medical treatment of meningiomas. In addition, these results suggest that EGF may be involved in the genesis and/or progression of meningiomas.