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.

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.

Effect of epidermal growth factor on glioma cell growth, migration, and invasion in vitro.

Effects of epidermal growth factor (EGF) and an antibody (Ab-528) reactive against the binding site for EGF on human EGF receptors were studied on multicellular tumor spheroids obtained from three human glioma cell lines with high (D-37 MG), medium (D-247 MG), and low (D-263 MG) levels of EGF receptor expression. The D-247 MG and D-263 MG spheroids grew slowly or not at all in the absence of EGF, while in the presence of EGF they were growth stimulated. Tumor cell migration, as measured by the spread of cells from spheroids on a plastic substratum, was increased by the addition of EGF for all three cell lines. Stimulation of migration could be blocked by a subsequent addition of Ab-528 to the medium at a concentration of 50 micrograms/ml. Invasiveness of glioma cell spheroids into fetal rat brain aggregates was related to EGF receptor expression; the two lines with medium to high receptor expression (D-247 MG and D-37 MG) were invasive, while the line with low EGF receptor expression (D-263 MG) was noninvasive, as assessed by an in vitro coculture assay. In the D-247 MG cell line, morphometry revealed EGF-enhanced invasiveness of the tumor cells. The addition of the Ab-528 to EGF-treated cocultures reduced invasion in both D-247 MG and D-37 MG cell lines. Antibody Ab-528 alone did not affect glioma cell growth or migration but did inhibit invasiveness. The present study suggests that, in brain tumors with an increased number of normal-sized Mr 170,000 EGF receptors, EGF or an EGF-like ligand such as transforming growth factor-alpha may selectively facilitate expansive tumor growth and tumor cell invasion. This effect may in part be blocked or retarded by specific antibodies to the EGF receptor.

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.

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.

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.

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.

Shunt failures and complications in adults as related to shunt type, diagnosis, and the experience of the surgeon.

Data from 95 adult patients (43 males, 52 females) treated with ventriculoperitoneal shunts during an 8-year period were analyzed to investigate risk factors in shunt surgery. All patients were seen in the authors' department and were grouped according to the cause or type of hydrocephalus. The operating surgeons were divided into two categories: specialists and residents. The shunts were classified as single- (Orbis-Sigma) or multicomponent (Holter or Hakim) systems. Two types of unfavorable events were recognized: complications and shunt malfunction. A total of 143 surgical procedures (implantations and revisions) were performed in the 95 patients; 24 patients had their shunts revised, and there were 13 complications (one fatal, five severe) resulting from the shunt surgery. The following observations were statistically significant: 1) patients with normal pressure hydrocephalus had no complications from shunt surgery; 2) the number of shunt malfunctions was lower in patients with intracranial hemorrhages than in the other groups; 3) residents performed a higher number of inadequate operations than did specialists; and 4) the infection rate was higher among patients operated on by residents. The choice of shunt type, the perioperative use of antibiotics, and the degree of surgical emergency were not correlated with complication or failure rates.

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.

Multicellular tumor spheroids in serum-free culture.

The serum-free culture of multicellular tumor spheroids from two rat (BT4c, BT5c) and two human (GaMg, D-54Mg) glioma cell lines is described. The spheroids were propagated in two different chemically defined media, showing differences in growth requirements between the human and rat cell lines. The spheroids from all the cell lines showed reduced growth rate as compared to spheroids maintained in serum supplemented culture. A change in spheroid morphology was observed for the D-54Mg cell line, indicated by a reduced occurrence of microvilli, increased pyknosis and cellular granularity. The other spheroids maintained their morphology in serum-free culture. For the D-54 Mg spheroids, flow cytometric DNA measurements showed that the serum-free growth conditions caused a drop in the DNA S-phase (6.4% vs. 12.3% in serum supplemented cultures). The cell cycle distribution was unchanged for the other cell lines tested. The present study provides the basis for using multicellular tumor spheroids in biological studies which are dependent on a detailed control with chemical environment.

Invasive glioma cells in tissue culture.

Malignant human glioma is characterized by an uncontrolled cell proliferation and infiltrative growth into the brain. The mechanisms by which invasion occurs are poorly understood. Due to recent development in tissue culture methods, it is possible to study invasion in organotypic coculture systems consisting of glioma spheroids and reaggregated fetal brain cells. Spheroids from well-characterized continuous human glioma cell lines have been tested for invasiveness in this model, which also allows studies of the invasive capacity of glioma cells derived from biopsy material within a week after surgery. Invasion may furthermore be studied in chemically defined media. The methods of studying in vitro glioma invasiveness are reviewed, together with recent results which may throw light upon important mechanisms related to glioma invasion, at the peri- and extracellular level. Mechanisms of glioma cell invasion are discussed with emphasis on the interactive process between cells, growth factors, proteolytic enzymes and the extracellular matrix.

A metalloproteinase, capable of destroying cultured brain tissue isolated from rat glioma cells.

A continuous rat glioma cell line, BT5C, which causes severe invasion and tissue destruction when cocultured with fetal rat brain aggregates, secreted into the culture medium a metalloproteinase in a hMr latent (86000) and an lMr active (76000) isoform. Purified preparations of the enzyme were added to cultures of fetal rat brain aggregates, which were then examined by light and by scanning electron microscopy. After 48h of enzyme exposure, destruction of the neural tissue was observed. This was morphologically similar to the tissue destruction seen when BT5C spheroids were cocultured with brain aggregates. The protease had no effect on the morphology of BT 5C tumour spheroids. The report suggests a possible role of metalloproteinases in tissue degradation during brain tumour invasion.

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.

Interactions between human glioma cells and fetal rat brain aggregates studied in a chemically defined medium.

The in vitro invasive growth of two continuous human glioma cell lines (D-54Mg and GaMg) into aggregates of fetal rat brain cells is described. The tumor cells were first cultured as multicellular tumor spheroids and thereafter cocultured with brain aggregates in medium agar cultures. Two different types of culture media were used for the propagation of spheroids and for coculture experiments: Dulbecco's modified Eagle's medium supplemented with 10% newborn calf serum, and Costar SF-X chemically defined hybridoma medium. Both cell lines showed invasive growth into brain tissue in both types of media. Apart from progressive destruction caused by the malignant cells, the brain aggregates maintained characteristics of neural tissue. One cell line (D-54Mg) showed reduced invasiveness in chemically defined medium as measured with a grading system to quantify invasion. The coculture system may represent a basis for studying invasion of human glioma cells in brain tissue under defined chemical conditions.

[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.

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.

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.