Endovascular treatment of trigeminal neuralgia caused by arteriovenous malformation: is surgery really necessary?

A case is presented with secondary trigeminal neuralgia (TN) caused by an arteriovenous malformation (AVM) of the cerebellopontine cistern, which was detected by radiological work-up for planned microvascular decompression. An AVM surrounding the trigeminal nerve was demonstrated on thin-slice heavily T (2)-weighted 3D-sequence on magnetic resonance imaging (MRI) and confirmed by angiography. The first therapeutic step was endovascular embolization with complete obliteration of the AVM and cessation of pain. Nevertheless surgical excision was performed in order to remove compressive vessels and to prevent a recurrence of pain.

[Diagnostic and therapeutical considerations in the treatment of giant aneurysms]. / Diagnostik und Therapie der intrakraniellen Riesenaneurysmen.

The treatment of giant aneurysms requires a thorough surgical and endovascular planning as this entity is accompanied by complex vascular and blood flow particularities. Even in experienced neurovascular centers the clinical outcome varies considerably. Within a series of 1386 aneurysm patients 72 (5%) giant (>25 mm) aneurysms were treated in our institution. Their age ranged between 26 and 81 years (medium age 52 years). 22 patients were suffering of a subarachnoid hemorrhage (SAH). Additionally there were 50 patients with nerve palsies or unspecific symptoms due to unruptured giant aneurysms (UGA). Treatment modalities included surgical clipping (n = 35), balloon occlusion of the ICA (n = 12), endovascular coiling (n = 7) or a combined regimen of balloon occlusion, surgical clipping and EC-IC bypass (n = 8). 10 patients could not be treated on due to their high age or minor clinical status (H&H IV and V). 6 of 15 (40%) SAH-patients were discharged without any complaints compared to 26% (12 of 47 patients) in the group of unruptured aneurysms. 1 SAH-patients (7%) versus 13 UGA (28%) patients suffered persisting nerve palsies or minor neurological disorders. 32% (n = 15) of the UGA-patients were suffering of major neurological deficits and required further professional help. 5 patients remained in a vegetative state, 3 of these had been admitted with an incidental finding of an UGA. 6 of 15 (40%) SAH-patients died, 5 of them admitted with H&H grade IV or V. However only 3 of 47 (6%) UGA patients died. 2 of these had a fatal SAH before treatment, 1 underwent EC-IC bypass surgery with insufficient hemispheric vascularization followed by gross infarction. The clinical status and age of the patient are significant factors influencing treatment associated morbidity and mortality. The individual vascular situation may lead to a complex therapeutical regimen thereby predisposes higher complication rates. We believe that surgical clipping is the first choice of treatment allowing temporarily clipping and reconstruction of the normal anatomy by shrinking or/and reconstructive clipping while reducing the mass effect. Whereas endovascular coiling alone is less favorable due to the packing of the coils a combined endovascular and surgical approach have to be considered in selected cases.

Tamoxifen sensitivity-testing of glioblastomas: comparison of in vitro and in vivo results.

BACKGROUND: Only less than half of the patients with malignant gliomas respond to a continuous high dose Tamoxifen (TAM) and/or Carboplatin (CP)-treatment. Therefore, a method for predicting the efficacy of TAM-treatment would be desirable. METHODS: Paralleling a clinical study, the predictive value of in vitro-sensitivity testing of TAM and TAM's metabolite 4-OH-TAM in primary cultures of tumour explants from 15 of a total of 50 patients was examined. Additionally, the influence of TAM, 4-OH-TAM, and CP on the proliferation of established glioblastoma cell lines and of those explanted from athymic nude mice and re-established in cell culture was investigated. Human glioblastomas xenotransplanted subcutaneously into athymic nude mice and subsequently treated with TAM and/or CP were examined in a parallel in vivo-study. FINDINGS: TAM-chemosensitivity-testing of glioblastomas failed to predict the clinical response to TAM-treatment in our patients and did not correlate with the in vivo-TAM-response of tumours xenotransplanted into nude mice. TAM's and 4-OH-TAM's ability to inhibit growth of various glioblastoma cell lines in vitro in very similar concentrations was shown to be a consistent phenomenon which seems to be independent of the in vivo response in either patients or mice as previous hosts. However, CP's antiproliferative effect on glioblastomas in vivo was paralleled by respective in vitro results. Whereas TAM showed to mediate its in vitro antiproliferative effect by inducing apoptosis in most cell lines examined, CP-treatment lead to necrosis of cells. INTERPRETATION: Combining the results obtained from our human and mouse studies, it has to be postulated that host factors other than the sensitivity to TAM of the individual cell, determine the efficacy of TAM-treatment in vivo.

Tamoxifen-resistant glioma-cell sub-populations are characterized by increased migration and proliferation.

Multifocal tumor recurrence of glioblastomas occurs in up to 14% of patients. In a parallel phase-II-study investigating post-operative treatment with tamoxifen (TAM), carboplatin and radiation therapy for glioblastomas, 16 of 49 patients (33%) showed multifocal recurrence, which developed after a mean of 46 weeks, raising the question of an association with therapy. We studied the interrelation of proliferation and migration in the presence of different protein-kinase-C(PKC) inhibitors (TAM, staurosporine, hypericin) in 2 glioma cell lines. In addition, 3 cell lines were selected for TAM resistance by repeated cycles of treatment with sub-lethal concentrations of TAM. The proliferative capacity and the invasive potential of selected sub-populations were assessed using growth-curve experiments, monolayer migration, and cell-adhesion assays. Treatment with all PKC inhibitors tested resulted in a dose-dependent decrease of proliferation, while motility was altered only at significantly higher doses. Resistance to TAM occurred in all 3 selected cell lines. The TAM-resistant sub-populations showed significantly increased proliferation, migration and adhesion as compared with the parental (non-selected) cell line. The higher incidence of multifocal disease after TAM treatment was paralleled by increased migratory potential of TAM-treated cells in vitro.

Surgery, tamoxifen, carboplatin, and radiotherapy in the treatment of newly diagnosed glioblastoma patients.

A historically controlled phase II study was undertaken to investigate the efficacy and toxicity of a postoperative treatment consisting of high-dose continuous tamoxifen, carboplatin and radiotherapy in patients with newly diagnosed glioblastoma. Between 1995 and 1998, 50 patients with newly diagnosed glioblastomas underwent surgery and were subsequently treated with 200 mg day(-1) tamoxifen continuously, 3 cycles of carboplatin (300 mg m(-2)), and radiotherapy. Survival data for a historical control group were calculated from respective prognostic indices and were obtained from studies with comparable patient populations treated with operation and radiotherapy only. In our study, the median time to tumor progression was 30 weeks and the median survival time (MST) 55 weeks (95% confidence interval: 46-63 weeks). The MST of the control group (48 weeks) showed to be within this interval. In addition to already known prognostic factors in malignant gliomas (age, Karnofsky performance score, extent of tumor resection), the gender (females lived longer than males, p = 0.0025) showed to influence survival. Serious side effects (thrombosis, pulmonary embolism) occurred in 6 patients. A high incidence of multifocal tumor recurrences (33%), which might be related to study-treatment, was observed. In conclusion, the combined therapy failed to demonstrate a higher efficacy than standard treatment for glioblastoma patients.

[Suprasellar meningioma. A disease still frequently diagnosed too late]. / Das supraselläre Meningeom. Ein immer noch häufig sehr spät erkanntes Krankheitsbild.

BACKGROUND AND OBJECTIVE: Suprasellar meningioma continues to be diagnosed very late after the onset of first eye symptoms. This study was aimed at demonstrating the effect of delay on the long-term visual loss. PATIENTS AND METHODS: In the course of a retrospective study all 53 consecutive patients operated on for suprasellar meningioma from 1982 to 1991 were contacted (47 women, 6 men; average age 49.5 years) 46 of the 49 surviving consented to the follow-up investigation. The extent of preoperative visual loss, tumour size, presence of optic nerve atrophy and duration of visual loss, data that provide an indirect measure of how soon the correct diagnosis was made, were analysed with regard to their effect on long-term ophthalmological results. RESULTS: The mean period elapsing from onset of first visual symptoms to the definitive diagnosis of suprasellar meningioma was 22.3 months. The data showed that the long-term results were the worse the later the diagnosis was made. CONCLUSIONS: The commonly very late diagnosis of suprasellar meningioma as cause of visual loss is an international problem and is presumably due to the low incidence of the tumour (1-2 cases per 1 mill. population per year). If long-term results are to be improved, primary care doctors must be made aware of the differential diagnosis of visual loss caused by pressure from a tumour.

Suprasellar meningiomas--neurological and visual outcome at long-term follow-up in a homogeneous series of patients treated microsurgically.

Most of the previously published surgical series of suprasellar meningiomas have two disadvantages: (1) patients involved were treated within a relatively long time period, making analysis more difficult, (2) radiographic long term follow-up examinations with either CT- or MRI-scans were not performed. Both disadvantages were overcome in our retrospective clinical study, consisting of 50 consecutive patients with suprasellar meningiomas treated between 1982 and 1991. Radiological, ophthalmological, and neurological investigations were performed preoperatively, postoperatively and at long term follow-up (mean: 5.7 years). A radiologically confirmed radical tumour removal could be achieved in 84% of patients. Both, the peri-operative mortality (2%) and serious operative morbidity (6%) were low. However, 12% of patients developed late onset epilepsy. At long term follow-up, visual function was improved in 67%, unchanged in 9% and worsened in 24%. In more than 50% of patients the vision showed recovery over a longer time period than the first 10 days after operation. Radiographic control examinations revealed tumour recurrences in 2 patients (both asymptomatic) and progress of residual tumour in 5 patients (2 symptomatic, 3 asymptomatic). Since introduction of modern neurosurgery, a clear improvement in the surgical treatment of suprasellar meningiomas can be observed. However, the still long delay in diagnosing these tumours correctly prevents a further improvement of the ophthalmological results at long-term follow-up. Due to a relatively high rate of late onset epilepsy, anticonvulsive prophylaxis for 6 months seems to be justified. Regarding present preoperative diagnostic measures, ia-DSA seems only be indicated in patients with CT/MRI-scans, suspicious for tumourous narrowing or invasion of major cerebral arteries. In addition, we recommend radiographic control examinations at regular time intervals to confirm radical tumour removal and to detect the "ideal" point of time for renewed treatment.

Pituitary surgery in elderly patients with acromegaly.

Because of the common belief that there is an increase in surgical risk and morbidity involved in the surgical therapy of elderly patients with acromegaly, physicians tend to either neglect therapy altogether or choose radiation therapy combined with medical treatment. In consideration of the expected increasing number of elderly patients resulting from social structure change in the coming years, we decided to investigate the outcome in 15 patients with acromegaly (13 women and 2 men) older than 64 years (mean, 68.3 yr) at the time of surgery in the form of a retrospective study. Medical treatment using either dopamine agonists (9 patients) and/or octreotide (4 patients) were attempted in 11 patients. For various reasons, however, medical therapy could not be permanently continued in any of these patients. The mean preoperative growth hormone (GH)-plasma level without medical treatment was 47.4 +/- 64.2 (mean +/- standard deviation) micrograms/L. At the time of operation, 13 of 15 patients had additional diseases, which led to an increased anesthesiological risk. Transnasal tumor removal was performed without anesthesiological or surgical complications in all patients. The radicality of tumor removal was controlled intraoperatively by GH measurements in eight patients. There was no postoperative mortality or serious morbidity. Postoperative basal GH-plasma levels were normal (< 4.5 micrograms/L) in all patients. None of the 13 patients who participated in long-term follow-up examinations (mean, 4.2 yr) revealed signs of definite tumor recurrence. The mean GH-plasma level at follow-up was 1.6 +/- 0.9 (mean +/- standard deviation) micrograms/L. One patient died 2 years after the operation of causes unrelated to pituitary surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Gangliocytomas of the sellar region--a review.

Gangliocytomas are benign, slow growing neuronal tumors and are found for the most part in children and young adults. They are most often localized in either the spinal cord or the cerebral hemispheres. Gangliocytomas in the sellar region are extremely rare and only 43 such tumors (including 4 own cases) have ever been described in the literature. Although these tumors are genuine rarities without any epidemiological importance, they do provide some interesting information on tumorigenesis of pituitary adenomas: 65% of the sellar gangliocytomas are associated with a pituitary adenoma. 74% of patients with these tumors suffered hormonal oversecretion of at least one of the pituitary hormones (mostly growth hormone). With only one exception, the hypothalamic releasing hormone corresponding to the hormonal oversecretion syndrome could be demonstrated in the gangliocytoma immunohistochemically. Ultrastructural studies could demonstrate close cell to cell contacts between adenoma and gangliocytome cells. All these data support the hypothesis that chronic overstimulation by hypothalamic releasing hormones play a role in the development of hormone secreting pituitary adenomas. However, in contrast to sellar gangliocytemas, extrahypothalamic tumors secreting excessive hypothalamic hypophysiotropic hormones have never been associated with a pituitary adenoma. They have only been associated with pituitary cell hyperplasia. Therefore, the hypothesis can be made that hypothalamic releasing hormones only promote but do not initiate tumorigenesis of pituitary adenomas.

Hypophysitis in surgical and autoptical specimens.

We present the clinical and histological findings of 11 cases of inflammatory anterior pituitary lesions, 8 of which were obtained during surgery and 3 of which were obtained from autopsies. Additionally, we extended the conventional classification of pituitary inflammatory disease by the new entity " secondary hypophysitis". Of the surgically obtained specimens 5 consisted of inflammatory extension into the pituitary gland out of the surrounding tissue. In all of these patients the inflammation originated from an additional tumor in the sellar region (4 craniopharyngiomas, 1 prolactinoma). These will be referred to as "secondary hypophysitis", an entity which has not yet been mentioned in the literature. Of the remaining 6 cases, 2 were granulomatous hypophysitis, 2 pituitary abscesses, 1 lymphocytic hypophysitis, and 1 showed extensive scarring of the anterior pituitary lobe due to preceeding lymphocytic hypophysitis. At histological examination the basic structure of the anterior pituitary was maintained in all cases. Relative counts of hormone-producing cells were normal. In secondary hypophysitis, the affected area was composed of fibrous tissue and granulation tissue. B and T lymphocytes were present in equal amounts. Granulomas were not found. Inflammatory infiltrates, granulation tissue and fibroses were seen in different proportions. Based on our results and three other cases reported in the literature so far, we think that the presently used classification of pituitary inflammatory diseases lacks an entity which describes a non-abscess-forming inflammation of the pituitary gland originating from an associated pathological process. Therefore, we introduced the term secondary hypophysitis to describe this fourth entity of pituitary inflammatory disease.

Monozygotic twins not identical with respect to the existence of intracranial aneurysms: a case report.

The hypothesis that intracranial aneurysms are inherited is based on published accounts of aneurysms occurring in two or more members of the same family. This hypothesis has been strongly supported by rare cases of intracranial aneurysms in pairs of identical twins. Seven such pairs have been reported to date. In all pairs, both twins had intracranial aneurysms, most of them located at the same site. Only rarely did they appear at exact contralateral locations. In five pairs, both twins suffered from a subarachnoid hemorrhage (SAH). In one case, the asymptomatic twin underwent angiography and was treated before an SAH occurred. We now present the first pair of identical twins. One twin had an SAH and two intracranial aneurysms. The other was asymptomatic and showed no aneurysms with either three-dimensional magnetic resonance angiography or intra-arterial digital subtraction angiography. Based on epidemiologic data, we assume that there must be many unreported cases of identical twins with at least one twin suffering from SAH. Our case indicates that the trait of intracranial aneurysms is not inherited with complete penetrance, which might otherwise be assumed on the basis of all other accounts previously described in the literature. However, as long as the exact means of inheritance of intracranial aneurysms is not understood, we still recommend an angiographic examination of the asymptomatic identical twin in cases where the other sibling had already suffered from an aneurysmal SAH.

The anterior pituitary lobe in patients with cystic craniopharyngiomas: three cases of associated lymphocytic hypophysitis.

Specimens of the anterior pituitary lobe were investigated histologically in 28 craniopharyngioma patients operated on trans-sphenoidally. The pituitary glands in 3 patients revealed lymphocytic invasion giving a histological appearance typical of lymphocytic hypophysitis (incidence: 11%). At follow-up examination all three patients with associated lymphocytic hypophysitis had complete pituitary insufficiency, whereas only 36% of the craniopharyngioma patients without associated lymphocytic hypophysitis were in this poor postoperative endocrine state. The phenomenon of associated lymphocytic hypophysitis in craniopharyngioma patients has not been reported so far. This might be due to the fact that investigators have failed to systematically examine the anterior pituitary lobe in craniopharyngioma patients. The 60 cases of lymphocytic hypophysitis reported in the literature occurred, for the most part, in women during late pregnancy or shortly after delivery. An auto-immune origin is assumed in this type of inflammation. In contrast to this pathophysiological mechanism, we assume a local induction of inflammation resulting from the craniopharyngioma cyst in our 3 patients.

Combined sellar gangliocytoma and pituitary adenoma in acromegaly or Cushing's disease. A report of 3 cases.

Three cases of a composite sellar tumour composed of a gangliocytoma and an adenoma are presented. Two patients who showed acromegaly and hyperprolactinaemia had a gangliocytoma and a growth hormone (GH)-prolactin cell adenoma in close proximity. The gangliocytoma contained growth hormone-releasing hormone (GHRH) by immunohistochemistry. At the electron microscopical level, the gangliocytoma was characterized by numerous synaptic vesicles. The third patient, a child with Cushing's disease, presented a corticotropin-releasing hormone (CRH)-positive gangliocytoma in close contact with an adrenocorticotropic hormone (ACTH) secreting adenoma, the latter a typical densely granulated ACTH cell adenoma. Ultrastructurally, the gangliocytoma revealed synaptic vesicles and sparse secretory granules. The results suggest that gangliocytomas may promote the development of pituitary adenomas by hypersecretion of releasing hormones. Whereas 20 cases of sellar GHRH producing gangliocytomas in acromegaly are reported in the literature, the combination of a CRH-positive gangliocytoma and an ACTH cell adenoma in Cushing's disease is apparently the first case.

Cushing's disease in a child caused by a corticotropin-releasing hormone-secreting intrasellar gangliocytoma associated with an adrenocorticotropic hormone-secreting pituitary adenoma.

Cushing's disease resulting from intrasellar corticotropin-releasing hormone (CRH)-secreting gangliocytomas is very rare, and only two such cases have been reported in the literature to date. The authors present a third case in which an adrenocorticotropic hormone-secreting pituitary adenoma was found in addition to a gangliocytoma in a 10-year-old girl with clinical and endocrinological symptoms of Cushing's disease. Computed tomographic and magnetic resonance imaging scans showed a suprasellar and parasellar tumor. A green-colored, heterogeneous tumor and a small adenoma were removed transsphenoidally. Histological examination revealed a large gangliocytoma immunoreactive for CRH and a small, mucoid cell pituitary adenoma immunoreactive for ACTH. This is the first case of such a tumor causing Cushing's disease in a child. It might exemplify induction of an ACTH-secreting pituitary adenoma by means of chronic overstimulation of CRH.

Thiamine-deficient encephalopathy in association with aneurysmal subarachnoid hemorrhage: a case report.

An alcoholic man who was admitted with an acute onset of neck pain and confusion was diagnosed as suffering from a subarachnoid hemorrhage after rupture of an anterior communicating artery aneurysm. Additionally, he showed a bilateral 6th nerve palsy of variable extent. The postoperative course was complicated by pulmonary edema and adult respiratory distress syndrome. He died on Day 28 after admission. At autopsy, surprisingly, the concomitant diagnosis of acute thiamine-deficient encephalopathy was made. Thiamine had been given only in minimal amounts during hospitalization. We describe the striking clinicopathological features of this previously undocumented case and consider the relationship between the two central nervous diseases.

Autoradiographic demonstration of in vivo 125I-growth hormone-releasing hormone (GHRH) binding by human GH-secreting pituitary adenomas transplanted on athymic nude mice.

This study was designed for the purpose of investigating a method for in vivo tumor labelling of human GH (hGH) secreting pituitary adenomas. Pituitary adenoma tissue removed from four acromegalic patients was transplanted into 62 athymic nude mice. After positive GHRH stimulation tests 125I-GHRH(1-44) NH2 was injected intravenously (i.v.) in ten nude mice. 10 min after 125I-GHRH injection, the nude mice were sacrificed, the transplants excised and prepared for light microscopical autoradiography. The mouse pituitary and skeletal muscle specimens served as controls. After the i.v. injection of 125I-GHRH we observed a marked accumulation of silver grains within the adenoma tissue indicating tumor labelling. This study is a first step in investigating a new method for labelling small residues of hGH secreting pituitary adenomas intraoperatively.

Use of athymic nude mice for in vivo studies of human growth-hormone-secreting pituitary adenomas.

Human growth hormone (hGH)-secreting pituitary adenoma tissue of 31 acromegalic patients was transplanted subcutaneously onto 291 athymic nude mice. 37% of the transplanted adenoma fragments could be maintained vital up to 46 days. Histological examinations of the transplants revealed neither alterations in their morphological characteristics nor signs of growth. A maintenance or linear decline of hGH secretion of the transplants related to their vitality was observed by hGH radioimmunoassay. Estimation of graft vitality was improved by GH-releasing hormone (GHRH) stimulation in regular intervals. The rate of pituitary adenomas responding to GHRH was as high as in a major collective of acromegalic patients. Our method of positive selection of vital xenotransplanted hGH-secreting pituitary adenomas via hGH detection at regular intervals in combination with GHRH stimulation gives the opportunity of reliable in vivo research with these tumors.