Hydrocephalus shunt therapy: current titanium shunt valve implants obstructed by internal tissue proliferations identified as extracellular matrix membranes.

PURPOSE: Shunt valves, required for treatment of hydrocephalus, demand for high performance rates and lifelong excellent function. To overcome problems with traditional silicone materials, adjustable and gravity-adapted titanium valves were developed. Even modern shunt valve systems are still subject to occlusion. The aim of the present study was to investigate dysfunctional silicone and titanium valves for presence of cellular and proteinous materials inside the housings by means of histopathology. METHODS: A total of 19 explanted shunt valves from children between 2 and 182 months of age were investigated following dysfunction. After fixation in formalin and embedding in hard resin, slices were ground to a thickness of 5-30 µ. Besides standard histology, immunohistochemistry was performed using antibodies with markers for microglia, astrocytes, platelets, monocytes, and the proteins laminin, fibronectin, and collagen IV. RESULTS: Traces, layers, and plaques could be demonstrated in every investigated silicone or titanium valve with an implantation time of more than 6 days. Most of the tissue was found adjacent to silicone and titanium surfaces of the inner housing, the adjustment rotor, and ball-in-cone core. Markers for micro and astroglia stained positive in 40-60% of the specimen, mostly demonstrating a proteinous layer positive for laminin (80%), fibronectin (30%), and collagen IV (30%). CONCLUSIONS: Tissue reactions with formation of cellular and proteinous matrix components are common in obstructed silicone and titanium shunt valves. The tissue mimics astrocytic repair mechanisms genuine for basilar membrane matrix. The knowledge of these typical arachnoid patterns of colonization is a prerequisite for developing future shunt devices.

Infratentorial meningioma in an 8-year-old child as first sign of neurofibromatosis type 2.

Meningiomas are rare intracranial tumors in pediatric patients. In contrast to meningiomas in adults, childhood ones have a poorer prognosis because of their high growth potential and tendency to recur. Meningiomas are often associated with neurofibromatosis type 2 (NF2) which is an autosomal-dominant disorder. In contrast to adults who primarily present with symptoms due to vestibular tumors, the initial symptoms in children with NF2 are subtle skin tumors, posterior capsular cataracts, or neurological signs secondary to cranial nerve(s) schwannoma excluding vestibular nerve, and/or brainstem or spinal cord compression. Here we report on the clinical, radiological, and histological findings in an 8-year-old boy who was diagnosed with an isolated infratentorial meningioma and a novel splice site mutation in the NF2 gene. The same mutation was detected in the boy's mother who suffered from hearing loss and tinnitus due to a bilateral vestibular schwannoma. Our patient demonstrates the need for molecular testing for NF2 gene mutations even in isolated childhood meningiomas although they do not fulfill the clinical criteria of NF2.

First experiences with a 2.0-microm near infrared laser system for neuroendoscopy.

Nd:YAG, argon and diode lasers have been used in neurosurgical procedures including neuroendoscopy. However, many neurosurgeons are reluctant to use these lasers because of their inappropriate wavelength and uncontrollable tissue interaction, which has the potential to cause serious complications. Recently, a 2.0-microm near infrared laser with adequate wavelength and minimal tissue penetration became available. This laser was developed for endoscopic neurosurgical procedures. It is the aim of the study to report the initial experiences with this laser in neuroendoscopic procedures. We have performed 43 laser-assisted neuroendoscopic procedures [multicompartmental congenital, posthaemorrhagic or postinfectious hydrocephalus (n = 17), tumour biopsies (n = 6), rescue of fixed and allocated ventricular catheters (n = 2), endoscopic third ventriculostomy (ETV, n = 17) and aqueductoplasty (n = 1)] in 41 patients aged between 3 months and 80 years. The laser beam was delivered through a 365-microm bare silica fibre introduced through the working channel of a rigid endoscope. It was used for the opening of cysts, perforating the third ventricular floor, and for coagulation prior to and after biopsy. The therapeutic goals [creating unhindered cerebrospinal fluid (CSF) flow between cysts, ventricles and cisterns, sufficient tissue samples for histopathological diagnosis and catheter rescue] were achieved in 40 patients by the first and in 2 patients by a second neuroendoscopic operation. In one child, a CSF shunt was later required despite patency of the created stoma proven by magnetic resonance imaging (MRI). In another patient ETV was abandoned due to a tiny third ventricle. There was neither mortality nor transient or permanent morbidity. The authors conclude that the use of the 2.0-microm near infrared laser enables safe and effective procedures in neuroendoscopy.

Expression of glutathione S-transferase T1 (GSTT1) in human brain tumours.

Glutathione S-transferases (GSTs) play a central role in a number of metabolic processes. Glutathione S-transferase T1 (GSTT1) is a polymorphic cytosolic enzyme and a member of the theta class of GSTs. Typical substrates for GSTT1 are industrial compounds, such as dichloromethane and ethylene oxide. It has been shown that also chemotherapeutic drugs such as BCNU [i.e. 1,3-bis(2-chloroethyl)-1-nitrosourea] are efficiently inactivated by GSTT1. BCNU is a drug which is increasingly used locally in the chemotherapy of glioblastoma multiforme WHO grade IV. Therefore, if GSTT1 were expressed in neoplastic cells of brain tumours it could be a factor for chemoresistance. In order to clarify a possible role of GSTT1 in chemoresistance, as a first step, we localized this enzyme in malignant gliomas such as glioblastoma multiforme WHO grade IV and oligodendroglioma WHO grade II. Because of its polymorphism we first genotyped the samples for GSTT1 by PCR. Using in situ hybridization, we then demonstrated that GSTT1 transcripts are expressed in neoplastic cells of both tumour types. Immunohistochemistry revealed then that whereas neoplastic cells in glioblastoma multiforme WHO grade IV contain GSTT1, it was not localized in oligodendroglioma cells. Given the polymorphism of GSTT1 and its potential activity towards BCNU, the localization of GSTT1 in glioblastoma cells can be considered as a possible factor of non-homogeneous chemotherapy response among patients with different GSTT1 genotypes.

Piezoelectric bone surgery: a revolutionary technique for minimally invasive surgery in cranial base and spinal surgery? Technical note.

OBJECTIVE: Piezoelectric surgery represents an innovative, ultrasonic surgery technique for performing a safe and effective osteotomy or osteoplasty that contrasts with the traditional hard and soft tissue management methods with rotating instruments. METHODS: Because of its physical and mechanical properties, the definitive clinical advantage of piezoelectric bone surgery with regard to precision cutting lies in the sparing of vital neurovascular bundles or general soft tissue and better visualization of the surgical field, thus suggesting its great safety. Piezoelectric bone surgery has been previously described only in oral and maxillofacial operative procedures in adults. RESULTS: Five children between the age of 6 and 84 months were operated on for craniosynostosis, tethered cord, and an extraconal intraorbital tumor. The usefulness of piezoelectric bone surgery during neurosurgical procedures is presented for these cases. This technique is especially recommended when there are anatomic difficulties because of poor intraoperative visibility or the presence of delicate anatomic structures. CONCLUSION: The present preliminary report (comprising illustrative case reports) demonstrates and introduces for the first time the utility of piezoelectric bone surgery in cranial base and spinal surgery in children. Until now, there has been no documented neurosurgical experience of this technique even in adults.

Expression of tyrosine kinases FAK and Pyk2 in 331 human astrocytomas.

The progression of malignancy from astrocytomas to glioblastomas remains clinically as well as histopathologically unpredictable. The focal adhesion kinase (FAK) and the proline-rich tyrosine kinase (Pyk2) show a high expression in glioma cell lines and have an influence on increased cell proliferation and migration of glioma cells in vitro and in vivo. The aim of this study was to correlate the coexpression of FAK and Pyk2 to the WHO grade of malignancy in human astrocytomas. Immunohistochemical staining scores of FAK and Pyk2 were analyzed in 331 astrocytomas and correlated to each other and to the WHO grade. Significant coexpression of FAK and Pyk2 in astrocytomas was demonstrated. Pyk2 expression occurred much more frequently and with higher expression scores within the different WHO grades. Beyond this, a significant correlation between the WHO grade of malignancy of astrocytomas and the expression of FAK, as well as of Pyk2, was detected. This connection and the roles of these two tyrosine kinases in the progression of tumors should be confirmed by further studies.

Expression of focal adhesion kinase (p125 FAK) and proline-rich tyrosine kinase 2 (PYK2/CAKb) in cerebral metastases, correlation with VEGF-R-, ecNOS III-labelling and morphometric data.

BACKGROUND: Cerebral metastasis occurs in about 20% of all neurosurgical patients. Cerebral metastases have a typical spherical morphology with a common central necrosis and perifocal oedema. It has been proposed that oedema extension, tumour volumes and infiltrative behaviour are partially mediated by vascular endothelial growth factor (VEGF) and nitric oxide (NO). In several systemic tumour entities NO is suggested as a factor which influences the metastatic potential. VEGF has recently been reported to influence the matrix related migratory activity by interaction with focal adhesion kinase (p125FAK) and proline-rich tyrosine kinase beta (PYK2/CAK beta). Nitric oxide, which is produced in metastases by three different NOS isozymes is capable of antagonizing the binding of FAK to matrix integrins. NO, VEGF and FAK/PYK 2 are therefore considered to be important mediators of the cerebral metastatic incidence, growth, infiltration and oedema extension. The aim of our present study was to investigate the expression of p125FAK and the coexpression with PYK2/CAK beta, VEGF-receptor FLT-1, NOS isozymes NOS I-III, capillary density and the histology in 130 specimens of resected cerebral metastatic tumours. A further analysis was performed to morphometrically evaluate tumour and oedema volumes and to correlate the immunohistochemical data in a subgroup of 40 patients. MATERIALS AND METHODS: Cryosections (N = 130) of metastatic resections were investigated immunohistologically using a 4-step scoring evaluation for the expression of NOS I-III, VEGF-receptor FLT-1, and capillary vessel presence by endothelial Von-Willebrand-Factor (VWF) staining. Tumour and oedema extension was measured in preoperative MRI (N = 40) scans by an image-processing device (Kontron) and the ratios of oedema volumes to total tumour volumes were calculated. The data were analysed statistically (Spearman rank order correlation and Kruskal-Wallis ANOVA) and correlated with the clinical data. RESULTS: FAK immunoexpression was observed in 50% of the specimens (31.2% gradings 2 and 3). We observed a significant coexpression (p = 0.0001) with PYK 2 labelling which occurred frequently in 74% of the specimens (42% gradings 2 and 3). The VEGF receptor FLT-1 could be detected in 70% of them, 24% at higher expression values 2 and 3. The expression of NO synthase was frequently observed. NOS I was detected in 83.6% of the specimens, values 2 and 3 in 40.5%. NOS III, the endothelial isoform, was observed in 39.4% of the specimens (gradings 2 and 3) and inducible NOS II in 29.4% (grading 2 and 3) of them. Coexpressions were statistically significant for FAK and NOS III (Spearman p = 0.008) and FAK and VEGF-R (p = 0.03). The morphometric evaluation resulted in tumour volumes between 2.0 and 83 cm3 (mean 22.5 +/- 19.1 SD) with oedema ratios between 0 and 100% (mean 62.2 +/- 22.5 SD). FAK expression correlated significantly (p = 0.06) with tumour volumes and histology. CONCLUSION: The frequent histotypic occurrence of FAK and PYK2 in metastases could be an important factor in the modulation of metastatic capacity and infiltrative behaviour and might influence the disease course. Judging from its frequent expression PYK2 may generate the more relevant signals. A further aspect is the possible interaction with endothelial NOS III and VEGF receptor, which could be important for the infiltrative behaviour in a latent hypoxic scenery and environment.

The C1-C2 interface residue lysine 50 of pig kidney fructose-1, 6-bisphosphatase has a crucial role in the cooperative signal transmission of the AMP inhibition.

To understand the mechanism of signal propagation involved in the cooperative AMP inhibition of the homotetrameric enzyme pig-kidney fructose-1,6-bisphosphatase, Arg49 and Lys50 residues located at the C1-C2 interface of this enzyme were replaced using site-directed mutagenesis. The mutant enzymes Lys50Ala, Lys50Gln, Arg49Ala and Arg49Gln were expressed in Escherichia coli, purified to homogeneity and the initial rate kinetics were compared with the wild-type recombinant enzyme. The mutants exhibited kcat, Km and I50 values for fructose-2,6-bisphosphate that were similar to those of the wild-type enzyme. The kinetic mechanism of AMP inhibition with respect to Mg2+ was changed from competitive (wild-type) to noncompetitive in the mutant enzymes. The Lys50Ala and Lys50Gln mutants showed a biphasic behavior towards AMP, with total loss of cooperativity. In addition, in these mutants the mechanism of AMP inhibition with respect to fructose-1,6-bisphosphate changed from noncompetitive (wild-type) to uncompetitive. In contrast, AMP inhibition was strongly altered in Arg49Ala and Arg49Gln enzymes; the mutants had > 1000-fold lower AMP affinity relative to the wild-type enzyme and exhibited no AMP cooperativity. These studies strongly indicate that the C1-C2 interface is critical for propagation of the cooperative signal between the AMP sites on the different subunits and also in the mechanism of allosteric inhibition of the enzyme by AMP.

The influence of airway pressure changes on intracranial pressure (ICP) and the blood flow velocity in the middle cerebral artery (VMCA).

OBJECTIVE: Due to the exponential shape of the intracranial volume-pressure relation, simple measurement of epidural, parenchymal or intraventricular intracranial pressure (ICP) in traumatic brain injury (TBI) often fails to early recognize patients with a fulminant development of intracranial hypertension even during recently available methods of tissue PO2 and microdialysis measurements. One approach to this problem could be repetitive intracranial volume provocations to evaluate a trend of the intracranial elastance. Several previously published methods use invasive volume challenge through access to the cerebrospinal fluid (CSF). This pilot study describes changes in intracranial pressure due to variations of airway pressure with BIPAP ventilation maneuvers. PATIENTS AND METHODS: Ten patients with severe TBI were enrolled and completed the study. The inclusion was based on radiologic signs due to TBI in the first CT-scan and the clinical indication for insertion of an ICP monitoring device. Patients with elevated ICP above 20 mm Hg were excluded. The epidural ICP response together with haemodynamic parameters in relation to defined airway pressure changes (delta PAW) was detected. The influence of the duration of delta PAW was evaluated additionally. Data of central venous pressure (CVP), ICP, mean arterial pressure (MAP), cerebral perfusion pressure (CPP), airway pressure (PAW) and blood flow velocity of the middle cerebral artery (VMCA) were analyzed on the basis of differences between the maximum (inspiration) and minimum PAW values (expiration). RESULTS: Elevations of PAW in the range of 20 to 35 cm H2O resulted in changes of the ICPmean from 4.1 to 6.0 mm Hg (r = 0.9, p < 0.05). A correlation was estimated for the changes of systolic arterial pressure (Part) and CPPmean due to PAW variations which ranged between 4.5 and 11.6 mm Hg (r = 0.99, p < 0.05). Concerning the transcranial doppler measurements the data of changes of the blood flow velocity of the middle cerebral artery (VMCA) revealed a positive correlation to PAW with a r = 0.99, p < 0.05. CONCLUSIONS: Elevation of the venous outflow resistance and a transient increase in cardiac output have to be considered as mechanisms for transduction of transthoracic pressure changes to intracranial pressure variations. We conclude, that trends of changes in elastance can be derived from intermittent airway pressure variations. This can be useful in easy and on line dynamic monitoring of ICP in traumatic brain injury.

Expression of nitric oxide synthase isozymes (NOS I-III) by immunohistochemistry and DNA in situ hybridization. Correlation with macrophage presence, vascular endothelial growth factor (VEGF) and oedema volumetric data in 220 glioblastomas.

BACKGROUND: Nitric oxide (NO) is synthesized from arginine by three different isozymes of nitric oxide synthase (NOS I-III). NO has been identified as a powerful metabolite of vascular smooth muscle cell function, cerebral blood circulation and oedema induction. NOS induction by different cytokines has been shown previously in glioblastoma cell cultures and NOS III expression due to astrocytoma grading has been shown in several tumors recently. The aim of the present study was to study the coexpression of NOS I-III, macrophage and capillary presence with VEGF, EGF and their receptors and to investigate a possible mechanism in peritumoral oedema generation. MATERIALS AND METHODS: We have investigated the expression (4-grade values, blinded assay by two observers) of NOS I-III together with those of VEGF, VEGF- R (Flt-1), EGF-R1, von-Willebrand-factor (VWF) and a pan-macrophage marker (Ki-M1P) immunohistochemically in tumor specimens from 220 patients and performed tumor volume morphometry by image analysis in a subgroup of 32 cases to test for any correlation with the peritumoral oedema volumes. Inducible NOS II was further investigated by in situ labelling with a DNA oligonucleotide probe cocktail. RESULTS: All of the specimens revealed some NOS expression, NOS II was expressed in macrophages, microglia and endothelial cells, NOS III and I was localized in glioblastoma cells, NOS III in endothelial cells as well. The highest degrees of expression were observed in 46% (NOS I), 22% (NOS II) and 75% (NOS III) of all specimens. Inducible NOS II in any expression grade was observed in 47.5% of the specimens. Significant correlations were observed for the expression of the macrophage marker Ki-M1P with NOS II (p = 0.024), endothelial NOS III with NOS I (p = 0.0003), VEGF-R1 with NOS II (p = 0.0008) and NOS III (p = 0.011) The oedema volumes could not be correlated significantly with NOS or VEGF-R1 expression values but with those of endothelial staining (p = 0.02). We observed a trend towards higher Ki-M1P expression values together with higher oedema volume extensions. In situ hybridization demonstrated reaction products in endothelial and perivascular regions and sometimes scattered throughout the specimens revealing the labelling of macrophages. CONCLUSIONS: The main source of NO is NOS I and NOS III. The latter is located in endothelial cells and glioblastoma cells. The expression of NOS II in glioblastomas is restricted to infiltrating macrophages. NOS II and III expressions were observed significantly together with that of VEGF-R1. Neither NOS I-III nor VEGF-R expression could be correlated with the extension of the peritumoral oedema.

Oedema extension in cerebral metastasis and correlation with the expression of nitric oxide synthase isozymes (NOS I-III).

BACKGROUND: The development of a peritumoral oedema is a common radiological sign in preoperative CT- and MRI scans of patients with cerebral metastasis. Large tumours can be accompanied by a marginally extended oedema and vice versa. Several cytokines (VEGF) have been identified as mediators of vascular induction and permeability. Transmitters such as nitric oxide (NO) have been identified as specific mediators of vascular dilation and tumour blood flow in primary brain tumours in which different NOS isozymes (NOS I and III) are induced as a result of the latent hypoxic metabolic scenery. Other authors have considered NO as an endothelial stabilising metabolite. Inducible NOS II is expressed by microglia and macrophages invading during tumour growth. At present, no data exist on NO synthesising enzymes in cerebral metastasis. MATERIALS AND PATIENTS: Cryosections (N = 96) of metastatic resections were investigated immunohistologically using a 4-step grading evaluation for the expression of NOS I-III, VEGF-receptor FLT-1, a pan-macrophage marker Ki-M1P, and capillary vessel presence by endothelial Von-Willebrand-Factor staining. The tumour and oedema extension was measured in preoperative MRI scans by an image processing device (Kontron) and calculated for the ratios of oedema volumes to total tumour volumes. The data were analysed statistically (Pearson Chi2 and Kruskal-Wallis analysis of variances) and correlated with the clinical data. Inducible NOS II was further investigated by in situ hybridization with a (4x30 mer) DNA oligoprobe cocktail. RESULTS: Between 1987 and 1996 289 patients in our department suffered from a metastatic disease in the brain or spinal cord. In 96 cases resected tumour material was processed for the immunohistological investigation. The age distribution ranged from 14 to 85 years with a median age of 58 years. The mean duration of symptoms before diagnosis was estimated as 53 days. The expression of NO synthase was frequently observed. NOS I was detected in 83.6%, gradings 2 and 3 in 40.5% of them. NOS III, the endothelial isoform, was observed in 39.4% (gradings 2 and 3), inducible NOS II in 29.4% (grading 2 and 3) of the specimens. The VEGF receptor FLT-1 could be detected in 70% of them, 24% in higher expression 2 and 3. The pan macrophage marker Ki-M1P was observed in 72% of all cases. Fifty seven percent of the specimens exhibited strong labelling with antibodies against VWF. Coexpressions were statistically significant for the VEGF receptor and NOS I-III (p < 0.01), Ki-M1P and NOS I and II (p < 0.05). A negative correlation was detected for the oedema index (oedema volume/total volume) and the labelling data for NOS III (r = -0.44, p = 0.13) and VEGF-R (r = -0.42, p = 0.022). No correlation existed for Ki-M1P, VWF and NOS I. CONCLUSIONS: The objective of the study was to investigate oedema morphometry, expression of NOS I-III and VEGF-R, presence of capillary vessels and macrophages in cerebral metastasis. A further aim was to investigate a putative oedema induction by NO producing isozymes. Nitric oxide synthase expression was statistically significantly correlated with the expression of the VEGF receptor and the presence of macrophages and microglia. There was a negative correlation between oedema extension and the presence of NOS III and VEGF-R. The results seem to indicate a specific oedema modulating role of NO in cerebral metastasis.

Suppression of kinetic AMP cooperativity of fructose-1,6-bisphosphatase by carbamoylation of lysine 50.

Selective treatment of pig kidney fructose 1,6-bisphosphatase with cyanate leads to the formation of an active carbamoylated derivative that shows no cooperative interaction between the AMP-binding sites, but completely retains the sensitivity to the inhibitor. By an exhaustive carbamoylation of the enzyme a derivative is formed that has a complete loss of cooperativity and a decrease of sensitivity to AMP. It was proposed that the observed changes of allosteric properties were due to the chemical modification of two lysine residues per enzyme subunit [Slebe et al. (1983), J. Protein Chem. 2, 437-443]. Studies of the temperature dependence of AMP sensitivity and the interaction with Cibacron Blue Sepharose of carbamoylated fructose 1,6-bisphosphatase derivatives indicate that the lysine residue involved in AMP sensitivity is located at the allosteric AMP site, while the lysine residue involved in AMP cooperativity is at a distinct location. Using [14C]cyanate, we identified both lysine residues in the primary structure of the enzyme; Lys50 is essential for AMP cooperativity and Lys112 appears to be the reactive residue involved in the AMP sensitivity. According to the fructose 1,6-bisphosphatase crystal structure, Lys50 is strategically positioned at the C1-C2 interface, near the molecular center of the tetramer, and Lys112 is in the AMP-binding site. The results reported here, combined with the structural data of the enzyme, strongly suggest that the C1-C2 interface is critical for the propagation of the allosteric signal among the AMP sites on different subunits.

Expression of CD 73 (ecto-5'-nucleotidase) in 165 glioblastomas by immunohistochemistry and electronmicroscopic histochemistry.

BACKGROUND: CD 73 (5'-nucleotidase) is an ectoenzyme, which is expressed on normal and neoplastic glial plasma membranes. The enzyme binds to intracellular filamentous actin and the extracellular matrix proteins laminin and fibronectin. CD 73 is a signalling pathway metabolite in the immune response of lymphocytes. The ectoenzyme catalyzes the conversion of purine and pyrimidine ribo- and deoxyribo-nucleoside monophosphates (AMP, GMP, IMP) and leads to elevation of the corresponding nucleosides (adenosine) in the extracellular space and might therefore modulate neuronal signalling and vascular perfusion. CD 73 has also been called a cellular motility factor. There is an increasing amount of evidence for the modulatory role of PKC-mediated CD 73 activity in ischemia, regeneration and repair, glioma cell proliferation and a possible invasion promoting feature of the ectoenzyme. The aim of the present study was to investigate the expression patterns of CD 73 together with the labelling of PKC and EGFR. The latter is known as a marker for primary glioblastomas. PATIENTS AND METHODS: We investigated the expression of CD 73 in 165 glioblastoma specimens together with the expression patterns of PKC and EGFR by immunocytochemistry on cryosections with a 4-step grading evaluation by two independent observers. CD 73 was further investigated morphologically by electron-microscopic histochemistry in cell cultures of glioblastoma specimens. RESULTS: With these methods it was possible to demonstrate a dense labelling pattern of glioblastoma specimens with anti-CD 73. 95.7% of the glioblastomas were identified with staining products, 63% with labelling grades 2 and 3. The dense staining of the endoplasmatic reticulum, vesicles, caveolar structures and glial membranes was demonstrated by electron-microscopic histochemistry. Some free enzymatic activity was located bound to the ECM components. We observed a significant coexpressions of CD 73 with PKC (p = 0.001) and CD 73 with EGFR (p = 0.022), which is a prospective marker for a high rate of early recurrency. CONCLUSIONS: The CD 73 activity was densely distributed on the membranes of glioblastoma cells in vivo and in cell cultures. The electron-microscopic histochemical studies could demonstrate enzymatic activity at the cell membranes and in vesicular structures and caveolae. Free staining deposits located on ECM components may result in a migration- and infiltration-promoting activity. The CD 73 expression could be correlated with the expression grades of PKC and EGFR. The latter has been identified as a prognostic factor which is expressed mainly on primary glioblastomas. PKC is a known tumour metabolite in several proliferation promoting pathways of EGF receptor signalling.

Elevated cerebral perfusion pressure and low colloid osmotic pressure as a risk factor for subdural space-occupying hygromas?

BACKGROUND: Space-occupying subdural hygromas are a late complication of severe traumatic brain injury (TBI) and may delay the patient's recovery. To evaluate the risk factors involved, we performed a semiretrospective, -prospective analysis of three groups of patients, which differed with regard to the techniques used in the management of their cerebral perfusion pressure (CPP) and colloid osmotic pressure (COP) to determine the occurrence of space-occupying subdural hygromas. PATIENTS AND METHODS: Between 1989 and 1997 we examined 696 patients after a severe TBI: Group 1. 1989-1994 mean CPP: 67 (elevated for therapeutic reasons by catecholamines, if necessary), mean COP: 19. Group 2. January 1995-October 1996, mean CPP: 77, mean COP: 20. Group 3. November 1996-December 1997, mean CPP: 79, mean COP: 23 (elevated for therapeutic reasons by infusions of colloids). The groups were comparable for other criteria. RESULTS: Compared to Group 1, Group 2, with a high CPP but lower COP, showed a significantly higher (p < 0.01; chi2-test with correction of Yates) percentage of posttraumatic subdural hygromas with space-occupying aspects, clinical signs of bradycardia, hypertension and impaired consciousness requiring surgery (Group 1: 1.75%; Group 2: 10.46%; Group 3: 0%). In Group 3 we saw no patient with a space-occupying hygroma. CONCLUSION: We conclude that iatrogenic elevated CPP, which has been reported to be helpful in preventing secondary ischemic damage after a severe TBI, may be harmful to a patient if the COP is not maintained within physiological ranges.

Brain metastases in neurosurgery: indications, surgical procedures and outcome.

Between July 1987 and June 1995, 1897 patients underwent operative therapeutic procedures for resection of tumours of the central nervous system in our department. 252 patients (13.3%) suffered from a metastatic disease in the brain or spinal cord. They comprised 113 females and 139 males. The age distribution ranged between 14 and 86 years with a median age of 58 years. The histology of resected tumours was distributed among lung-(54), breast-(33), melanoma-(27), kidney-(23) and prostate carcinoma (19). Other metastizing tumour sites were present in 96 cases. The age distribution of breast carcinoma ranged between 32 and 78 years with the median located at 54 years. 5 patients underwent a surgical resection of a local recurrence with a median latency of 9 months. Median survival time was estimated as 13 months with a one year survival of 63%. The aim of the study was to reflect on incidences, therapeutic procedures and outcome of brain metastatis.

Optimized evaluation of a pulsed 2.09 microns holmium:YAG laser impact on the rat brain and 3 D-histomorphometry of the collateral damage.

Since more than 20 years CO2 and Nd:YAG lasers are established in the microsurgery of the nervous system. CO2 lasers can be used handheld, but may be focused on the target area by mirror optics and sideports of the operating microscope's micromanipulator. Nd:YAG lasers have the disadvantage of deep penetration into the brain and provocation of a large collateral damage. The need is for a fibre conducted solid system for surgery in delicate areas as for brain stem surgery. Fibre conduction of near infrared lasers allows better exposure of the target area compared to hollow wave guides or mirror equipment. Fibres can be tapered and modified according to the purpose. The holmium:YAG (Ho:YAG) laser has acquired interest by introducing the system into microsurgery of parenchymal tissue. They have not been proven yet sufficiently for neurosurgical tasks. The effort to minimalize the collateral tissue damage has to be maximalized in the surgery of nervous tissue and functional low redundant brain stem or spinal cord tissue. Volumetric data may be more precise in comparison to depth and width data of the laser lesion even when the different levels of the tissue interaction have to be analyzed for estimation of the real side effects in nervous tissue. We have used 50-800 ml delivered Ho:YAG single pulses in cortical areas of Sprague-Dawley rats and investigated the different lesion zones by volumetric data. The functional lesion zone was detected and measured by immunohistological staining of the heat shock protein HSP 72. For further reduction of the focus area, we have used tapered 400 to 200 microns fibres.

Glycerol gangliotomy of the second dorsal cervical root in rats: an experimental study to evaluate a minimal invasive approach for the treatment of the chronic cervicogenic headache.

Glycerol is a known agent in the therapy of chronic tic douloureux. It has been used for about 20 years in percutaneous, retrogasserian minimal-invasive rhizotomy, although the pharmacological mechanism of the pain relief involved remains unclear. To investigate glycerol treatment as a possible replacement for invasive approaches in the therapy of chronic cervicogenic headaches, we performed an experimental study on the pathomorphologic action of anhydrous glycerol injection into the second upper cervical dorsal root ganglion (DRG) of rats. Glycerol injections into the second cervical ganglion were investigated light- and electron-microscopically in a series of 40 rats for survival times of up to 30 days. We detected an unspecific overall effect on sensory neurons and satellite cells, as well as on myelinated and unmyelinated axons and Schwann cells. This could be detected after 5 days and sometimes led to degeneration of most of the neurons. Contralateral saline injections as a control showed no morphological effects. The loss of afferent fiber connections to the posterior horn of the myelon could be detected by immunohistochemical labeling of reactive astrocytes. Our results show a glycerol-induced deterioration of the cytoarchitecture of the neurons and their glial satellite cells. The effects on the ganglion cells appear to have been mediated by membrane disturbances and loss of glial integrity. These observations are contrary to previously reported results indicating the specific effect of glycerol on thin myelinated sensory axons.

[Trigeminal neuralgia as symptom of an infratentorial space-occupying process]. / Symptomatische Trigeminusneuralgie als Symptom einer infratentorialen Raumforderung.

UNLABELLED: Despite excellent technical means of imaging the posterior fossa by magnetic resonance imaging (MRI), some infratentorial space-occupying processes still remain undiscovered, especially if they present only slight symptoms or imitate typical different diseases. METHODS: We analysed the data of 334 patients who were admitted because of infratentorial space-occupying processes in the years 1986 to 1995. RESULTS: There were six patients with trigeminal neuralgia caused by infratentorial tumors. In only one was the tumour previously diagnosed. All suffered from tic douloureux; two had undergone operative treatment. Mean latency from first symptoms until diagnosis was 48 months. On admission all patients presented at least slight neurological deficits. Postoperatively, the patients remained pain-free. CONCLUSION: Because the prognosis of operative treatment and the occurrence of postoperative deficits depend on tumour size, we advocate MRI examination in every patient presenting tic douloureux, even without additional neurological signs.