Surgery for high-grade gliomas in the aging.

OBJECTIVE: High-grade glioma (HGG) is the commonest primary brain tumor in adults. We prospectively assessed outcome following surgery and adjuvant treatment for HGG in older patients. MATERIALS AND METHODS: Patients ≥ 60 years undergoing craniotomies for gliomas WHO grade 3 and 4 at Oslo and Haukeland University Hospitals 2008-2009 were included (n = 80). Outcome was assessed at six months, and overall mortality evaluated at two years. RESULTS: Forty-two males and 38 females of median age 68.5 (60-83) years were included, 35% attended a follow-up appointment at six months. Surgical mortality was 1.3%. Surgical morbidity included neurological sequela (10%), post-operative hematomas (3.8%) and hydrocephalus (1.3%). Median overall survival was 8.4 months and significantly increased by adjuvant radiochemotherapy. In univariate survival analyses, age ≥ 80 years, subtotal resection, American Society of Anesthesiology (ASA) scores 3-4, Karnofsky performance scale (KPS) < 70, and mini-mental state examination (MMSE) score < 25 significantly reduced survival. CONCLUSIONS: Surgical treatment of HGG carries low mortality and acceptable morbidity in patients aged ≥ 60 years. There is improved survival following bimodal adjuvant treatment. Maximum tumor resection should be attempted. Treatment might be less beneficial in patients aged ≥ 80 years and in those with poor pre-operative function.

Outcome following surgery for intracranial meningiomas in the aging.

OBJECTIVE: To prospectively assess mortality, morbidity and the functional and symptomatic outcome following intracranial surgery for meningiomas in elderly patients at two neurosurgical institutions in Norway. METHODS: Patients ≥60 years who underwent craniotomies for intracranial meningiomas at Oslo University Hospital and Haukeland University Hospital in 2008 and 2009 were included (n = 54). Outcome was assessed at 6 months. RESULTS: Thirty-five females and 19 males of median age 70 (60-84) years were assessed pre- and post-operatively, 87% attended follow-up at 6 months. The surgical mortality rate was 5.6% at 30 days and 7.4% at 3 and 6 months. The rates of complications were: post-operative hematomas 5.6%, deep venous thrombosis 1.9%, osteitis 1.9%, cerebrospinal fluid disturbances 13.0% and neurological sequelae 13.0%. Surgery resulted in a significant improvement in the MMSE score, with a further 14.9% obtaining scores of ≥25 without a significant change in the level of independence according to the Karnofsky performance scale. QoL assessments showed good functioning post-operatively compared to other cancer patient groups, yet slightly reduced when compared to data from the general population. CONCLUSION: In our series, we found that meningioma surgery in the aging patient carries a higher risk of mortality and morbidity compared to intracranial tumor surgery in general. Our findings indicate, however, that the survivors have improved cognitive function and acceptable QoL, and we did not see any significant decrease in the proportion of independent patients according to the KPS.

Analysis of vestibular schwannoma size in multiple dimensions: a comparative cohort study of different measurement techniques.

OBJECTIVES: In this volumetric study of the vestibular schwannoma, we evaluated the accuracy and reliability of several approximation methods that are in use, and determined the minimum volume difference that needs to be measured for it to be attributable to an actual difference rather than a retest error. We also found empirical proportionality coefficients for the different methods. DESIGN/SETTING AND PARTICIPANTS: Methodological study with investigation of three different VS measurement methods compared to a reference method that was based on serial slice volume estimates. These volume estimates were based on: (i) one single diameter, (ii) three orthogonal diameters or (iii) the maximal slice area. Altogether 252 T1-weighted MRI images with gadolinium contrast, from 139 VS patients, were examined. MAIN OUTCOME MEASURES: The retest errors, in terms of relative percentages, were determined by undertaking repeated measurements on 63 scans for each method. Intraclass correlation coefficients were used to assess the agreement between each of the approximation methods and the reference method. The tendency for approximation methods to systematically overestimate/underestimate different-sized tumours was also assessed, with the help of Bland-Altman plots. RESULTS: The most commonly used approximation method, the maximum diameter, was the least reliable measurement method and has inherent weaknesses that need to be considered. This includes greater retest errors than area-based measurements (25% and 15%, respectively), and that it was the only approximation method that could not easily be converted into volumetric units. Area-based measurements can furthermore be more reliable for smaller volume differences than diameter-based measurements. CONCLUSIONS: All our findings suggest that the maximum diameter should not be used as an approximation method. We propose the use of measurement modalities that take into account growth in multiple dimensions instead.

Treatment of vestibular schwannomas. Why, when and how?

Sporadic vestibular schwannoma (VS) causes unilateral hearing loss, tinnitus, vertigo and unsteadiness. In many cases, the tumour size may remain unchanged for many years following diagnosis, which is typically made by MRI. In the majority of cases the tumour is small, leaving the clinician and patient with the options of either serial scanning or active treatment by gamma knife radiosurgery (GKR) or microneurosurgery. Despite the vast number of published treatment reports, comparative studies are few, and evidence is no better than class III (May, 2006). The predominant clinical endpoints of VS treatment include tumour control, facial nerve function and hearing preservation. Less focus has been put on symptom relief and health-related quality of life (QOL). It is uncertain if treating a small tumour leaves the patient with a better chance of obtaining relief from future hearing loss, vertigo or tinnitus than by observing it without treatment. Recent data indicate that QOL is reduced in untreated VS patients, and may differ between patients who have been operated and patients treated with GKR. In the present paper we review the natural course and complaints of untreated VS patients, and the treatment alternatives and results. Furthermore, we review the literature concerning quality of life in patients with VS. Finally, we present our experience with a management strategy applied to more than 300 cases since 2001.

Treatment of chronic subdural hematoma by burr-hole craniostomy in adults: influence of some factors on postoperative recurrence.

BACKGROUND: The study was conducted to determine the causative factors in the postoperative recurrence (PR) of chronic subdural haematomas (CSDHs) and to evaluate the efficacy of surgery in adults enrolled in this trial. METHODS: 99 patients with 121 CSDHs, who were operated on between January 1999 and December 2001, were studied. We evaluated the PR rate related to anamnestic, clinical, surgical and neuroradiological imaging variables. In addition, we reviewed the number and the type of repeated operations, complications of surgery and the outcomes at one, three and 12 months. FINDINGS: 82.6% of lesions were successfully treated following the initial evacuation, and 95.9% of lesions following a second procedure. The PR rate was 14.9%. A significantly high PR rate was found to be associated with separated type, frontal base type, a midline displacement >5 mm and the presence of acute subdural clots in cranial base type on CT scans obtained within four days postsurgery. The interval from head trauma to initial surgery <60 days, the maximum width of subdural space >10 mm and massive collection of air in the subdural space tended to give a high PR rate. The PR rate associated with the homogeneous type of CSDHs was significantly low.Age, sex, cause of CSDH, anticoagulant therapy, preoperative neurological presentation, concomitant disease, variables on preoperative CT scans, and surgical factors such as the extent of the surgical procedure, use of drainage, duration and volume of drainage were not significantly associated with PR rate. CONCLUSIONS: It is important to identify factors leading to a high or a low PR rate in the treatment of CSDHs because this may help to select appropriate surgical procedures and postoperative management to treat this condition efficiently.

Neurosurgical treatment of meningiomas in children and young adults.

OBJECT: We studied the frequency, functional outcome, association with neurofibromatosis (NF) and relapse in patients operated on for meningiomas at age 0-20 years in three Norwegian centers between 1972 and 1999. METHODS: Information was collected by examining case notes and histology records, conducting telephone interviews and performing new radiological investigations. Twenty-seven patients were identified. Five had NF, and all 5 developed multiple tumors. In non-NF patients, relapse occurred in 2 out of 19 who underwent total tumor resection, and in all 3 whose surgery was non-radical. There was 1 postsurgical death, and no other major complications. Most patients had few complaints or none at all resulting from their previous tumor or treatment. CONCLUSIONS: Meningiomas without NF have a good prognosis in children and young adults if the tumor can be removed radically. However, relapse can occur many years after the primary operation.

lacZ-neoR transfected glioma cells in syngeneic rats: growth pattern and characterization of the host immune response against cells transplanted inside and outside the CNS.

The rat glioma cell lines BT4C and BT4Cn were stably transfected with the bacterial lacZ-neomycin resistance (neoR) gene construct. Both transfected (BT4ClacZ and BT4CnlacZ) and untransfected cell lines were injected intracerebrally and subcutaneously into rats. Survival time, morphology, growth rate and immunological properties of the tumors were studied. Survival time was significantly prolonged after intracerebral implantation of the transfected cell lines. No similar response was found in nude rats, indicating an immunological response towards the lacZ-neoR-transfected cells in immunocompetent animals. Morphological observations showed that the lacZ-neoR-transfected gliomas were smaller and had a distinct boundary with the normal brain tissue, whereas the parental cell lines revealed a more diffuse growth pattern. Immunostaining showed a higher proportion of immunocompetent cells infiltrating the lacZ-neoR-transfected tumors. After s.c. injection, the lacZ-neoR-transfected BT4C cell line had a prolonged lag phase before assuming a growth rate similar to that of the parental cells. The BT4CnvlacZ tumors initially grew fastest, but then disappeared within 3 weeks. A similar response was observed with mock-transfected tumor cells. A (3)HTdR-incorporation assay on spleen cells from rats transplanted s.c. with BT4CnvlacZ cells showed a 10-fold increase in cell activation as compared with rats with BT4Cn tumors. A humoral response towards the transfected cells was verified by Western-blot analyses.

Alginate-encapsulated producer cells: a potential new approach for the treatment of malignant brain tumors.

In recent years gene therapy has evolved as a new treatment for brain tumors, where genetically engineered cells can be used to deliver specific substances to target cells. However, clinical success has been limited due to insufficient gene transfer, lack of prolonged gene expression, and immunorejection of producer cells. These obstacles may be overcome by encapsulating producer cells into immunoisolating substances such as alginate. This may provide a stable in situ delivery system of specific proteins, which can interfere with tumor growth and differentiation. This article represents a fundamental study describing the in vitro and the in vivo behavior of alginate-encapsulated producer cells. The viability and cell cycle distribution of encapsulated NIH 3T3 cells was studied by confocal laser scanning microscopy (CLSM) and by flow cytometry. The CLSM study showed a high viability of the encapsulated NIH 3T3 cells during 9 weeks in culture. The flow cytometric analysis revealed a change in cellular ploidy after 1 week in culture, with normalization in ploidy after 3 and 9 weeks. The production of the bacterial E. coli beta-galactosidase in alginate-encapsulated BT4CnVlacZ cells was studied by x-gal staining, and the cells expressed prolonged beta-galactosidase activity. H528 hybridoma cells producing monoclonal antibodies (mAbs) against the human epidermal growth factor receptor (EGFR) were encapsulated in alginate, and the mAb release was determined. The release of mAbs stabilized around 400 ng/ml/h after 12 days in vitro. To actually demonstrate that alginate-encapsulated H528 cells potentially inhibit a heterogeneous glioma cell population, cell migration from human GaMg glioma spheroids was studied during stimulation with EGF in the presence of encapsulated H528 cells. The migration in vitro was totally inhibited in the presence of H528 encapsulated cells. Alginate beads with H528 cells were also implanted into rat brains, and after 9 weeks the distribution of mAbs within the brain was studied by immunohistochemistry. It is shown that the alginate entrapped H528 cells produce mAbs inside the brain for prolonged periods and that the mAbs are distributed within all CSF compartments. Encapsulated producer cells represent a potential delivery system for specific proteins to brain tumors. Different producer cells may be encapsulated in alginate to target phenotypic features and microenvironmental factors, which may influence the progressive growth of brain tumors.

Laminin expression by glial fibrillary acidic protein positive cells in human gliomas.

Extracellular matrix components are regarded as important substrates for invasive tumor cells. The present work focuses on the expression of laminin in the brain in response to invading brain tumors. Biopsies obtained from tissue macroscopically evaluated as the border zone between tumor and normal brain, in 5 patients undergoing surgery for glioblastoma multiforme, were examined by immunocytochemistry and scanning confocal microscopy for the expression of laminin and glial fibrillary acidic protein. Laminin was mainly found in all the specimens associated with the basal lamina of blood vessels, but a variable degree of punctate laminin deposits were also observed in the parenchyma not associated with blood vessels. In the specimens with substantial deposits, scanning confocal microscopy showed that some of the laminin co-localized with intracellular glial fibrillary acidic protein. Punctate deposits of laminin were also seen in an intracranial BT4C rat glioma model, where it was particularly abundant in the brain/tumor confrontation zone. Previous in vitro studies have shown that laminin, among several extracellular matrix components, represent a highly permissive substrate for glioma cell migration. The presented results indicate that laminin can be produced by glial fibrillary acidic protein positive cells during glioma cell invasion in humans. This glycoprotein may thus represent one important substrate among many, which contribute to the invasive phenotype of gliomas.

Retroviral transfection of the lacZ gene from Liz-9 packaging cells to glioma spheroids.

Despite the development of numerous vectors for gene transfection to gliomas, patient survival length remains unaffected in clinical trials. For glioma gene therapy to be successful, the extent of gene transfer to the solid tumor tissue has to be high. In the present work we review some of the vector types and strategies so far utilized in experimental and clinical glioma gene therapy. Since gene transfer efficacy into solid glioma tissue is unknown for many vectors, we studied the gene transfer efficacy into multicellular spheroids derived from a human glioma cell line GaMg as well as into spheroids derived from human glioma biopsies (glioblastoma multiforme, GBM). A replication deficient retroviral vector from the Liz 9 packaging cell line was used for transfer of the bacterial beta-galactosidase lacZ gene into the target tissue. Gene transfer was obtained by adding medium containing virus from the producer cells to the target tissue. The experiments were also conducted with EGF (epidermal growth factor) added to the medium. The data show that the transfection rate ranged from 0-4.5% where the transfection efficacy was higher in spheroids after the addition of EGF. Most of the transfected cells were found at the surface, but transfected cells could also be observed in the center of the spheroids. We conclude that using this vector system, the transfection efficacy was low, even if the number of replicating cells was increased by adding EGF. The findings are consistent, and may partly explain, the lack of effect using this vector system during in vivo studies.

Extracellular matrix-induced cell migration from glioblastoma biopsy specimens in vitro.

The present knowledge about the interaction between the extracellular matrix (ECM) and gliomas is mostly based on studies of permanent cell lines. Since such cultures have undergone an extensive clonal selection in vitro, the experimental results obtained may be quite different from those obtained from studies on true biopsy specimens. The present work demonstrates how different ECM components affect tumor cell migration from human glioblastoma specimens grown as biopsy sample spheroids. Biopsy specimens from 12 glioblastomas and 1 gemistocytic astrocytoma were included in this study. Spheroids were directly initiated from the biopsy specimens, and after 3-4 weeks in culture, they were used in a migration assay. A custom-made filtered medium, where the high molecular weight (>100 kDa) proteins were removed, was supplemented with the following ECM components: laminin, fibronectin, collagen type IV and vitronectin. The cell migration was negligible when spheroids were propagated in the filtered medium. The ECM components as well as complete DMEM evoked strong stimulatory effects on different biopsy specimens. Opposed to that observed earlier for permanent glioma cell lines, highly variable responses were observed between the different biopsy samples on the various ECM components. In general, correlation analyses revealed that specimens that were strongly stimulated by laminin were also stimulated strongly by fibronectin, collagen type IV and vitronectin. This suggests that the capacity to migrate as a response to ECM was confined more to each biopsy specimen than to any specific ECM component. Since biopsy sample spheroids, as original tumors, consist of different cell types, an immunohistochemical characterization of the migrating cells was also performed. Anti-glial fibrillary acidic protein (GFAP) staining revealed both GFAP-positive and -negative migrating cells. Immunostaining for von Willebrand factor and CD11b indicated that the migrating cells were neither endothelial nor microglial cells. This study, therefore, indicates that migratory responses of glioma biopsy specimens to different ECM components is much more heterogeneous than that observed earlier for cell lines. Furthermore, the presented findings support the notion that gliomas may utilize different cell surface receptors for their migration, depending on the cell substrates available.

Dynamic determination of human glioma invasion in vitro.

OBJECT: The goal of this study was to evaluate whether there is any relationship between survival of patients with brain tumor and tumor proliferation or tumor invasion in vitro. METHODS: Samples of freshly resected brain tumors from 14 patients with glioblastoma multiforme (GBM) were directly grown as three-dimensional multicellular spheroids. The tumor spheroids were cocultured with fetal rat brain cell aggregates (BCAs), used to represent an organotypical normal brain tissue model. Before the coculture, the tumor spheroids and the BCAs were stained with two different carbocyanine dyes, 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) and 3,3'-dioctadecycloxacarbocyanine perchlorate (DiO), respectively. During the coculture, confocal laser scanning microscopy allowed a sequential analysis of tumor cell invasion by visualizing dynamic aspects of the invasive process. Single cocultures were examined at three different time points (24, 48, and 96 hours). During the observation period there was a change in the structural morphology of the cocultures, with a progressive decrease in BCA volume. Furthermore, the scanning confocal micrographs revealed a bidirectional movement of tumor cells and normal cells into brain and tumor tissue, respectively. It is also shown that there is a considerable variation in the rate of BCA destruction in cocultures of glioma spheroids generated directly from biopsy specimens. This variation is seen both between spheroids generated from the same biopsy as well as between spheroids that are grown from different biopsy specimens. Cell proliferation measured by Ki-67 immunohistochemical analysis of biopsy samples obtained in the same patients revealed a correlation between tumor cell proliferation and tissue destruction of the BCAs, as determined by a reduction in BCA volume (p = 0.0338). No correlation was found when survival was related to the same parameters (p > 0.05). CONCLUSIONS: The present work provides a model for quick and efficient assessment of dynamic interactions between tumor and normal brain tissue shortly after surgery.

Expression of annexin II in glioma cell lines and in brain tumor biopsies.

Annexin II is a calcium and phospholipid binding protein and a substrate for protein-tyrosine kinases. Increased levels of annexin II are observed in various cancer cells and tissues, and the molecule has been proposed as a marker of malignancy in vivo. Annexin II was expressed in four glioma cell lines (D-54MG, D-37MG, U251MG and GaMG), as determined by Western blot analyses, immunofluorescence staining and flow cytometric measurements. In addition, annexin II expression was also found in cryostat sections obtained from 15 consecutive brain tumor biopsies: Ten were histologically classified as glioblastomas, one as an astrocytoma, two as meningiomas and two as brain metastases. Cultured spheroids from the glioma cell lines and from three of the glioblastoma biopsies showed lower levels of annexin II, than found in the monolayers of the cell lines and in the freshly cut biopsies. The annexin II expression of the cell lines were not found to be related to their proliferative, migratory or invasive properties. These findings indicate that although annexin II may serve as a marker of malignancy in vivo, its expression can be reduced in vitro, and appear unrelated to malignant features of glioma cell lines.

Stimulation of extracellular matrix components in the normal brain by invading glioma cells.

Malignant gliomas are characterized by an extensive invasion of tumor cells into the normal brain parenchyma. A substantial amount of data indicates that cell movement in general is regulated by specific interactions between extracellular matrix components and specific cell-surface receptors. In the present work, multicellular spheroids from 4 human glioma cell lines (U-373Mg, A-172Mg, U-251Mg and HF-66) were confronted with normal rat brain cell aggregates in vitro, which resulted in a progressive invasion of tumor cells into the brain aggregates. The co-cultures were then sectioned and immuno-stained for specific extracellular matrix components (laminin, fibronectin and collagen type IV) and for specific cell-surface receptors which bind to these components (integrins beta1, beta4, alpha3, alpha6). In addition, flow-cytometric measurements and Northern blot analyses showed expression of several different integrins within the cell lines. The alpha3 subunit was expressed strongly in all cell lines. Whereas the beta1 subunit was expressed weakly in exponentially growing monolayer cultures, it showed a pronounced expression in multicellular spheroids, indicating that the integrin expression may vary depending on the micro-environment within a tumor. Furthermore, normal brain tissue was able to produce laminin when confronted with the glioma cells, which also was observed for fibronectin and collagen type IV. The relevance of our observations to the in vivo situation was investigated further by immuno-staining 5 human glioma biopsy samples for laminin. In some areas of the tumors, specific deposits of laminin were observed. In conclusion, we have shown that normal brain tissue has the ability to produce extracellular matrix components, such as laminin, collagen type IV and fibronectin, when confronted with invading glioma cells. Our results show that the glioma cells express specific integrins which can interact with these extracellular matrix components. Such interactions may facilitate tumor cell migration and invasion.

Syringomyelia treated with a nonvalved syringoperitoneal shunt: a follow-up study.

OBJECTIVE: Eighteen patients with syringomyelia received nonvalved syringoperitoneal shunts during the years 1987 through 1996. In 15 cases, the fistulae were multicompartmental, either separated by segments of normal cord or septated. METHOD: Even in the multicystic cases, only one syringeal catheter was introduced, usually into the caudalmost cavity. Access to the fistula was obtained via a midline myelotomy, which was performed in an area at which the spinal cord overlying the fistula was at its thinnest. RESULTS: The progressive clinical course of syringomyelia was arrested in all patients. Surgery resulted in improvement for 11 patients. Five patients remained unchanged without further progression. Two patients became worse as the result of new deficits caused by surgery. In four patients, the myelotomy lead to new but discrete sensory loss of minor importance. Postoperative magnetic resonance images showed a rapid and persistent collapse of all fistulae in all patients. CONCLUSIONS: We conclude that syringoperitoneal shunting is favorable in patients with large fistulae. In patients with Chiari malformations, the procedure may be a second alternative to foramen magnum decompression.

Tumor cell invasion and angiogenesis in the central nervous system.

Tumor cell growth and invasion within the CNS imply complex interactions among malignant cells, neural cells, and endothelial cells. Various in vitro assays have been developed to study tumor cell invasion that includes the use of cocultures between tumor spheroids and organotypic cultures of normal brain tissue. Furthermore, various animal models have been developed to study biologic characteristics of brain tumors. At present, there is evidence that several growth factors are involved in both endothelial and tumor cell proliferation, whereas the interrelationship between glioma growth and invasion is less well established. It is also emerging that the process of invasion is characterized by dynamic interactions between the extracellular matrix, proteases, and specific cell surface receptors. The dissemination of tumor cells within the CNS also involves a passive component where single tumor cells may follow specific pathways mediated by the constant flow of cerebrospinal fluid.

Role of high molecular weight extracellular matrix proteins in glioma cell migration.

Malignant human gliomas are characterized by an uncontrolled cell proliferation and infiltrative growth within the brain. Complete surgical removal is difficult due to disseminated tumour cells, and the fundamental mechanisms responsible for this spread are poorly understood. An extensive tumour cell movement along blood vessels is frequently observed and this may be due to specific interactions between tumour cell surface receptors and specific extracellular matrix (ECM) components present in conjunction with vascular elements. In order to investigate the influence of ECM on glioma cell migration, three different human glioma cell lines (U-373 MG, A-172 MG and HF-66) were exposed to known ECM components of the basement membrane (laminin, fibronectin and collagen type IV). Cell migration from multicellular spheroids was studied, using a custom-made medium which was prepared by removing the high molecular weight protein fraction (>100 kDa) from newborn calf serum by ultrafiltration. To this medium, the specific ECM components were added. For two of the cell lines (A-172 MG and U-373 MG), laminin was the most potent stimulator of glioma cell migration; the effect of laminin exceeded that evoked by ordinary serum-supplemented medium. For the HF-66 cell line, fibronectin was the most potent stimulator of migration. Western blot analysis showed that the A-172 MG and HF-66 cell lines expressed low amounts of laminin compared with U-373 MG, which showed extensive intrinsic synthesis of this ligand. U-373 MG was the only cell line that migrated in pure filtered medium. The cells stimulated by fibronectin expressed a different morphology from those stimulated by laminin suggesting that specific ECM-receptor binding may activate different cytoskeletal components within the cells. Furthermore, it was shown that there was no difference in the amount of protein synthesis between cells grown in filtered medium and in filtered medium supplemented with different ECM components. This suggests that ECM-induced cell migration is not dependent on a high level of protein synthesis. It is also shown that alpha3 integrin, which is a receptor-subunit for laminin, fibronectin and collagen type IV, was highly expressed in all cell lines. This study indicates that glioma cells need serum proteins with a molecular weight >100 kDa to migrate in vitro, and that laminin and fibronectin play an important role in this process.

Cognitive function in patients with Parkinson's disease undergoing stereotaxic thalamotomy.

OBJECTIVE: To determine whether thalamotomy leads to cognitive disturbances in patients with Parkinson's disease. METHODS: A total of 53 patients with Parkinson's disease undergoing stereotaxic ventrolateral thalamotomy for tremor and rigidity were tested for cognitive functions before and after surgery. The cognitive functions investigated involved visuospatial perception and memory. verbal memory, attention shift, and executive functions including set maintenance and shift. A neuropsychological test battery was used that contained the Wisconsin card sorting test, Street completion test, Stroop test, a dichotic memory listening test, and a facial recognition test. RESULTS: Clinically, a good or moderately good effect on parkinsonian symptoms was obtained in 50 patients. The neuropsychological investigations showed that the patients were impaired compared with healthy age matched control subjects on most tests, showing slight improvement postoperatively on verbal memory and visuospatial perception. No major differences were found between tests before and after operation, and there were no significant differences between patients undergoing surgery in the right or in the left thalamus. CONCLUSION: The study indicates that ventrolateral thalamotomy does not reduce the cognitive capacity in this group of patients.

[Subarachnoid hemorrhage. Severe consequences of delayed diagnosis]. / Subaraknoidalblødning. Alvorlige konsekvenser ved forsinket diagnose.

A total of 123 patients with subarachnoid haemorrhage were admitted to the Department of Neurosurgery, Haukeland Hospital, during the years 1990-93. In 16 patients, there was a delay from the first haemorrhage until diagnosis and treatment. In eight patients, the delay was caused by incorrect medical diagnosis, while two patients did not seek medical attention immediately after onset of symptoms. In the remaining six patients, the delay was caused by both patient and physician. In all but one patient, the first symptom was an unusually severe acute headache which in some cases was accompanied by nausea and vomiting, in others not. Altogether nine patients suffered renewed bleeding, and three patients died. Three patients showed neurological impairment postoperatively. The article deals with the importance of early diagnosis in patients with subarachnoid bleeding, and suggests how these patients should be handled by their primary doctors and at the hospitals to which they are referred.

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.