Search

Objective. Adjuvant systemic chemotherapy increases survival of primary malignant glioma patients beyond 12–18 months. The only interstitial chemotherapy treatment approved for malignant glioma is Gliadel® wafer containing carmustine (BCNU) placed in the resection cavity at surgery. Analysis of a large trial by Westphal and colleagues (n = 240) showed a 29% risk reduction ( P = 0.03) in the BCNU wafer-treated group over the course of the 30-month trial. Long-term follow-up of these patients was undertaken to determine the survival benefit at 2 and 3 years. Methods. Survival proportions for the placebo and treatment groups over the 56-month study were estimated by the Kaplan-Meier method. Multiple-regression analyses using the Cox proportional hazards model included prognostic factors of age, KPS, and tumor type. A secondary analysis was conducted for 207 GBM patients. Results. Of the 59 patients available for long-term follow-up, 11 were alive at 56 months: 9 had received BCNU wafers and 2 had received placebo wafers. Median survival of patients treated with BCNU wafers was 13.8 months vs 11.6 months in placebo-treated patients ( P = 0.017) with a hazard ratio of 0.73 ( P = 0.018), representing a 27% significant risk reduction. This survival advantage was maintained at 1, 2, and 3 years and was statistically significant ( P = 0.01) at 3 years. Two of 207 GBM patients remained alive at the end of the follow-up period, both in the BCNU wafer-treated group. Conclusion. Malignant glioma patients treated with BCNU wafers at the time of initial surgery in combination with radiation therapy demonstrated a survival advantage at 2 and 3 years follow-up compared with placebo. [ABSTRACT FROM AUTHOR]

Highlights the 12th European Congress of Neurosurgery in Lisbon, Portugal. Techniques in the treatment of arteriovenous malformation and aneurysms; Ethical aspects of selection for admission to intensive treatment and for withdrawal of treatment of patients with a severe head injury; Gene expression profiles of human gliomas and their clinical significance as tumor classifiers; Limits of skull base surgery for tumors; Use of intraoperative fluorescence as a guide to the resection of a malignant glioma; Development of oncolytic virus therapy; Management of spinal cord tumors with emphasis on the distinction between glial and vascular types.

Summary. Introduction: The case of a 38-year old man with a histologically benign choroid plexus papilloma arising within the fourth ventricle with en plaque growth around the brain stem and medulla is described in detail. Up to this point this particular growth pattern has not been published and is a rare presentation for this tumour. Clinical Presentation: The patient presented with a 1.5 year history of headache, nausea, and vomiting in the morning. Additional symptoms like blurred vision and gait ataxia lead to hospital admission. MRI demonstrated a homogeneously contrast-enhancing tumour completely filling the fourth ventricle and subsequent obstructive hydrocephalus. In addition Gd enhancement encasing the brain stem, the lower aspect of the medulla and the conus medullaris was seen suggesting a disseminated ependymoma or medulloblastoma. Intervention: An extensive resection of the tumour in the fourth ventricle and CP angle was performed. Infiltrative growth into the structures of the left CP angle and into the rhomboid fossa hampered complete removal. Surprisingly histological examination revealed a well-differentiated papillary choroid plexus papilloma without signs of anaplasia. On follow up imaging the Gd enhancement encasing the pons vanished completely. A growing cyst adjacent to a small tumour residuum left behind on the floor of the fourth ventricle led to re-operation after 8 months with complete removal. Discussion: This case presents several biological, neuroradiological and surgical aspects which make it noteworthy and we hope that the informations provided add to the understanding of these tumours, expand the differential diagnostic thinking of lesions which present with diffuse arachnoid Gd enhancement upon first presentation. [ABSTRACT FROM AUTHOR]

We report a series of 26 patients affected by a Chiari I malformation treated at our department between 1987 and 1993. All patients underwent pre- and postoperative evaluation by magnetic resonance imaging (MRI). Sequential perioperative motor evoked potential (MEP) recordings were performed in 8 patients. The preoperative symptoms can be divided into four subgroups: cephalgias (84.6%), cranial nerve deficits (69.2%), motor deficits (76.9%), sensory deficits (73%). Twenty-five out of 26 patients underwent craniovertebral decompression, 1 a transoral anterior decompression. One patient died 2 months after surgery because of progressive pulmonary failure. We registered following postoperative complications: transient hypoglossal palsy (1 case), vertigo (2 cases), meningitis (1 case), minor CSF leaks (3 cases). Cephalgias subsided in 17 and improved in 4 out of 22 patients. Cranial nerve deficits improved in 8 and were stabilized in 7 out of 18 patients. A limited recovery of trigeminal function was possibly due to nuclear lesions. Five patients whose vestibular disturbances were not relieved by surgery were put on a course of carbazepine. Vertigo resolved in one case and in two others improved. While hypesthesia improved after decompression, the other sensory deficits were stabilized in 5% of the patients. Spasticity improved in 12 out of 18 patients, but weakness only in 7 out of 17 patients. Motor disturbances ewre always detected by MEP-recording. MEP-characteristics were not specific, resembling those of patients with other intra-, extramedullary myelopathies. Functional recovery was not matched by an improvement of the MEP parameters. MEP may be used as a tool for survellance of patients whose clinical findings are not progressive and are not at first surgical candidates. [ABSTRACT FROM AUTHOR]

Five cultured human glioma cell lines were investigated for their reaction to prostaglandin (PG) D 2 and E 2. In all cases a suppressive effect on DNA synthesis as assessed byH-thymidine incorporation was seen with all test substances as early as six hours after the addition of the compounds in doses of usually 10 M. A dose response curve was generated in four cases and showed an estimated ED 50 of about 5 · 10 M. The effect was most pronounced at 12 hours after which the cultures began to recover except those which had been incubated with PGD 2. In those cultures which had been exposed to PGD 2 virtually no thymidine incorporation was seen after 24 hours and as long as 72 hours. In another set of experiments, the effect of PGD 2, PGE 2, two synthetic PGD 2 analogues, with a chlorine substitution in position 9 (DACl) or with a fluoride substitution in position 9 (DAF) and a synthetic prostacyclin-analogue (Iloprost) was investigated after single and repeated addition of the compounds. A second administration after 12 hours of incubation did not result in a further decrease inH-thymidine incorporation like that observed during that first incubation period. In general the cells recovered after 24 hours total incubation time except those which had received PGD 2 or repeated doses of PGE 2. Only in those cells which had been treated with PGD 2, an almost complete blockade ofH-thymidine incorporation was seen even after the single administration. Parallel evaluation of the cells by flow cytometry showed effects on cell cycle distribution at different times of the incubation. After 12 hours cells began to accumulate in G2/M at levels of approximately twice control, the effect being the least pronounced for PGD 2. For this compound we observed a threefold increase in cells in the S phase. After 24 hours the cell cycle distribution had normalized for all compounds except PGD 2 where the 'arrest' of cells in G2/M persisted to be about 2-3-fold control level until the end of the experiment. Our data suggest, that also in cultured human glioma cells, prostaglandins are effective in suppressing cellular DNA synthesis. Although the effect of PGD 2 can be achieved to some extent by PGE 2 and the analogues which are more stable to dehydrogenases and the metabolic conversion into other biologically active homologues, PGD 2 appears to have a unique quality of action, becoming apparent 24 hours after administration. [ABSTRACT FROM AUTHOR]

Equilibrium binding assays of EGF were performed on confluent cultures of 12 human meningiomas at early passage. In all meningeomas complete binding curves were obtained and the resulting ED 50 values ranged between 0.5 and 6.3 nM. In four cases (ED 50 values ranging from 1.5 nM to 3.0 nM) where saturation analysis was performed, the sites were saturable at similar levels (7nM). In five cases additional experiments were undertaken to evaluate the biological response of cultured cells to EGF as assessed byH-thymidine incorporation. In all cases EGF was a potent stimulus and increasedH-thymidine incorporation by 2.5 to 6-fold. Functionally intact EGF receptors appear to be a regular feature of meningiomas in cell culture and appear not to be related to histological classification. [ABSTRACT FROM AUTHOR]

Cell suspensions of ACTH cell adenomas of 10 patients with Nelson's syndrome were investigated for in-vitro secretion of ACTH. Two incubation systems, one using incubation beakers and the other a superfusion system, were employed. The cells were tested for their reactivity to lysine-vasopressin (LVP), cortisol, and combinations of both. LVP regularly provoked a rapid significant increase of ACTH secretion. The effect of cortisol was heterogeneous. Paradoxical initial stimulatory effects of cortisol were observed. There was a suppressive effect in some patients, which correlates to low proliferative activity in histological evaluation. In both systems a low secretory activity coincided with high proliferative activity in vivo. [ABSTRACT FROM AUTHOR]

Purpose: To analyze the reliability of the classification of intraoperative adverse events (ClassIntra) to reflect intraoperative complications of neurosurgical procedures and the potential to predict the postoperative outcome including the neurological performance. The ClassIntra classification was recently introduced and found to be reliable for assessing intraoperative adverse events and predicting postoperative complications across different surgical disciplines. Nevertheless, its potential role for neurosurgical procedures remains elusive., Methods: This is a prospective, monocentric cohort study assessing the ClassIntra in 422 adult patients who underwent a neurosurgical procedure and were hospitalized between July 1, 2021, to December 31, 2021. The primary outcome was the occurrence of intraoperative complications graded according to ClassIntra and the association with postoperative outcome reflected by the Clavien-Dindo classification and comprehensive complication index (CCI). The ClassIntra is defined as intraoperative adverse events as any deviation from the ideal course on a grading scale from grade 0 (no deviation) to grade V (intraoperative death) and was set at sign-out in agreement between neurosurgeon and anesthesiologist. Secondary outcomes were the neurological outcome after surgery as defined by Glasgow Coma Scale (GCS), modified Rankin scale (mRS), Neurologic Assessment in Neuro-Oncology (NANO) scale, National Institute Health of Strokes Scale (NIHSS), and Karnofsky Performance Score (KPS), and need for unscheduled brain scan., Results: Of 442 patients (mean [SD] age, 56.1 [16.2]; 235 [55.7%] women and 187 [44.3%] men) who underwent a neurosurgical procedure, 169 (40.0%) patients had an intraoperative adverse event (iAE) classified as ClassIntra I or higher. The NIHSS score at admission (OR, 1.29; 95% CI, 1.03-1.63, female gender (OR, 0.44; 95% CI, 0.23-0.84), extracranial procedures (OR, 0.17; 95% CI, 0.08-0.61), and emergency cases (OR, 2.84; 95% CI, 1.53-3.78) were independent risk factors for a more severe iAE. A ClassIntra ≥ II was associated with increased odds of postoperative complications classified as Clavien-Dindo (p < 0.01), neurological deterioration at discharge (p < 0.01), prolonged hospital (p < 0.01), and ICU stay (p < 0.01). For elective craniotomies, severity of ClassIntra was associated with the CCI (p < 0.01) and need for unscheduled CT or MRI scan (p < 0.01). The proportion of a ClassIntra ≥ II was significantly higher for emergent craniotomies (56.2%) and associated with in-hospital mortality, and an unfavorable neurological outcome (p < 0.01)., Conclusion: Findings of this study suggest that the ClassIntra is sensitive for assessing intraoperative adverse events and sufficient to identify patients with a higher risk for developing postoperative complications after a neurosurgical procedure., (© 2023. The Author(s).)

Background: Mechanical thrombectomies (MT) in stroke have changed the standard treatment regimen with a continuous increase of MTs during the last years. A subsequent reduction in the rates of decompressive craniectomies (DC) as well as a change in clinical characteristics of patients undergoing an additional DC after MT may be assumed. Therefore, objective of this study was to investigate the influence of nowadays regularly performed MT on patients undergoing DC., Methods: Patients with DC due to cerebral infarctions between January 2009 and January 2018 were included. Patients' clinical presentation and surgical parameters were collected retrospectively. Initial GCS and NIHSS, extent of the stroke, time interval from symptom onset to DC, and neurological outcome were compared between patients with and without thrombectomy., Results: A total of 5469 ischemic strokes were treated in the investigated period, leading to DC in 119 cases (2.2%). A decrease in the rate of performed DCs was recorded: in 2009, 2.8% of ischemic stroke patients underwent surgery compared to 1.9% in 2017. In the meantime, the number of MTs in our center has increased from 84 in 2014 to 160 in 2017. MT was performed in 32 patients prior to DC. No significant differences could be seen between the groups regarding age, initial NIHSS (median 18 in both groups, p = 0.81), extent of the infarctions prior to DC (median ASPECTS 0 in both groups, p = 0.87), time interval from symptom onset to DC, and neurological outcome., Conclusions: The introduction of routinely performed MT as part of the standard treatment regimen for ischemic stroke has led to a decrease in DCs. However, DC patients with and without MT showed no differences regarding their initial clinical criteria and outcome. These results suggest that earlier DC studies in patients with MCA infarction also apply for the collective of thrombectomized patients.

Background: Aneurysmal subarachnoid hemorrhage (SAH) as a serious type of stroke is frequently accompanied by a so-called initial thunderclap headache. However, the occurrence of burdensome long-term headache following SAH has never been studied in detail so far. The aim of this study was to determine the prevalence and characteristics of long-term burdensome headache in good-grade SAH patients as well as its relation to health-related quality of life (HR-QOL)., Methods: All SAH cases treated between January 2014 and December 2016 with preserved consciousness at hospital discharge were prospectively interviewed regarding burdensome headache in 2018. Study participants were subsequently scrutinized by means of a standardized postal survey comprising validated pain and HR-QOL questionnaires. A retrospective chart review provided data on the initial treatment., Results: A total of 93 out of 145 eligible SAH patients participated in the study (62 females). A total of 41% (38/93) of subjects indicated burdensome headache at follow-up (mean 32.6 ± 9.3 months). Comparison between patients with (HA+) and without long-term headache (HA-) revealed significantly younger mean age (47.9 ± 11.8 vs. 55.6 ± 10.3 years; p < .01) as well as more favorable neurological conditions (WFNS I/II: 95% vs. 75%; p = .03) in HA+ cases. The mean average headache of the HA+ group was 3.7 ± 2.3 (10-point numeric rating scale), and the mean maximum headache intensity was 5.7 ± 2.9. Pain and HR-QOL scores demonstrated profound alterations in HA+ compared to HA- patients., Conclusions: Our results suggest that a considerable proportion of SAH patients suffers from burdensome headache even years after the hemorrhage. Moreover, long-term headache is associated with reduced HR-QOL in these cases.

Background: The Woven EndoBridge (WEB) device has been increasingly used for the treatment of intracranial aneurysms after aneurysmal subarachnoid hemorrhage (SAH). Still, recent major clinical trials on patient management after SAH have defined WEB embolization as an exclusion criterion. In an analysis of an unselected patient cohort, we evaluate the early clinical course of SAH patients after WEB treatment compared to those treated with endovascular coiling or surgical clipping., Methods: Data of all patients with proven SAH who were either treated with a WEB device, coil embolization, or neurosurgical clipping between March 2015 and August 2018 was systematically reviewed. Clinical parameters on intensive care unit (ICU), medical history and mortality rates were evaluated and compared between the different treatment approaches., Results: Of all 201 patients included, 107 patients received endovascular coil embolization, 56 patients were treated with clipping and in 38 cases a WEB device was placed. The overall mortality was 17.9%. Thirteen patients (34.2%) in the WEB group had a Hunt and Hess grade > 3. Essential medical factors showed no clinically relevant differences between the treatment groups, and the analyzed blood parameters were predominantly within physiological limits without any relevant outliers. The Hunt and Hess grade but not the treatment modality was identified as independent risk-factor associated with ICU-mortality in the overall cohort (p < 0.001)., Conclusion: In this study, there was no difference in the early clinical course between those treated with WEB embolization, coil embolization, or neurosurgical clipping. Since WEB embolization is a valuable treatment alternative to coiling, it seems not justified to exclude this procedure from upcoming clinical SAH trials, yet the clinical long-term outcome, aneurysm occlusion, and retreatment rates have to be analyzed in further studies., Clinical Trial Registration Number: not applicable.

Background: Vancomycin and meropenem are frequently used as empiric treatment for ventriculitis. Penetration into the cerebrospinal fluid (CSF) depends on various factors with a high inter-individual variability. Because attaining and maintaining adequate concentrations of meropenem and vancomycin in the CSF is crucial for their bactericidal effect, we introduced a routine therapeutic drug monitoring (TDM) from CSF and serum for both antibiotics. We studied the antibiotic penetration into the CSF., Methods: Patient data including serum and CSF concentrations for meropenem and vancomycin were collected in a retrospective fashion. Antibiotic CSF penetration ratio was calculated for each patient. Antibiotics were administered by continuous infusion aiming for serum target concentrations of 20-30 mg/L for vancomycin and 16-32 mg/L for meropenem., Results: Twenty-two patients with 36 CSF/serum pairs for meropenem and 43 pairs for vancomycin were studied. No patient suffered from renal or liver insufficiency. Mean vancomycin serum concentration was 22 ± 8 mg/L and the mean CSF concentration 4.5 ± 2.6 mg/L. CSF penetration was 20 ± 11% (coefficient of determination (R 2 ) 0.02). For meropenem, the mean serum concentration was 30.7 ± 14.9 mg/L, mean CSF concentration 5.5 ± 5.2 mg/L, and a penetration of 18 ± 12%, R 2  = 0.42., Conclusion: Penetration of meropenem and vancomycin into the CSF is low while showing a high interindividual variability. Various patients in our study cohort were at risk for insufficient target attainment in CSF. Continuous administration of antibiotics under routine TDM appears to be a feasible and reasonable approach for optimization of intrathecal drug levels in patients suffering from ventriculitis. TDM might guide individual dosing adaptation and efforts to predict the CSF penetration of meropenem and vancomycin in cases of ventriculitis.

Background: Multidrug-resistant organisms (MDRO) are an increasing problem in critical care medicine. This study describes for the first time the rate and impact of MDRO in patients suffering from aneurysmal subarachnoid hemorrhage (SAH)., Methods: Anonymized data of SAH patients admitted to our institution from November 2010 to August 2017 were retrospectively reviewed. Patients with microbiological tests positive for MDRO were identified. Screening of MDRO was in consensus with national recommendations., Results: 449 SAH patients were reviewed with 18 patients (prevalence: four MDRO-positive patients per 100 SAH patients) having positive tests for MDRO during their hospital stay. The prevalence upon admission was 1.3 MDRO-positive patients per 100 patients. The acquisition rate was 1.1 MDRO-positive patients per 1000 hospital days. Patients positive for an MDRO had a significantly extended length of stay in intensive care (mean ± SD 26.7 ± 13.0 versus 18.4 ± 11.7 days, p = 0.004) and in hospital (mean ± SD 33.9 ± 12.4 versus 24.4 ± 12.6 days, p = 0.002). MDRO detection was associated with a significant prolonged duration of mechanical ventilation (median (IQR) 254.0 (14.9-632.8) versus 37.5 (3.3-277.0) hours, p = 0.02). There was no statistically significant effect on the Glasgow Outcome Scale (GOS) at discharge and at follow-up after 164.4 ± 113.0 days., Conclusions: MDRO positivity is present in 4% of aneurysmal SAH patients. It seems to be associated with a prolonged length of stay and prolonged duration of mechanical ventilation. The importance of infection control standards in neurointensive care units is emphasized.

Background: Early prediction of increased morbidity and mortality in aneurysmal subarachnoid hemorrhage (aSAH) remains crucial to improving patient management. Most prediction models lack external validation and focus on disease-specific items without considering physiological parameters and the past medical history. The aim was to assess the validity of the established Simplified Acute Physiology Score II (SAPS-II) in an aSAH cohort for the prediction of hospital mortality and to identify additional physiological and clinical predictors., Methods: The predictive value of SAPS-II for hospital mortality was assessed in a retrospective analysis of 263 consecutive patients with aSAH. Additional physiological and clinical parameters including the past medical history were analyzed by forward selection multivariate analysis to identify independent predictors of hospital mortality and to improve the prediction model., Results: The SAPS-II predicted hospital mortality with an area under the curve (AUC) of 0.834 with an odds ratio (OR) of 1.097 [95 % confidence interval 1.067-1.128) for each additional point. Forward selection multivariate analysis identified the Glasgow Coma Scale score (P < 0.001), history of chronic headache (P = 0.01) and medication with anticoagulants (P = 0.04) as independent predictors of hospital mortality. Adding these parameters to the SAPS-II, the AUC increased to 0.86., Conclusion: This study validates the predictive accuracy of SAPS-II for hospital mortality in aSAH patients. Additional parameters from the past medical history increase its predictive power. From a practical viewpoint, SAPS-II alone already represents a sufficient and powerful score to predict hospital mortality at an early time point and may help to improve patient management.

Background: Intraventricular hemorrhage (IVH) in patients suffering from aneurysmal subarachnoid hemorrhage (aSAH) is a known negative predictor. Scoring systems like Fisher, Le Roux, and original Graeb score (oGS) are established to quantify the volume of IVH. The aim of this study was to evaluate the validity of the recently introduced modified Graeb score (mGS) in patients with aSAH., Methods: A retrospective analysis of the validity of the oGS and mGS in 257 aSAH patients was performed to assess and compare the predictive value of hospital mortality, development of CHC, and early functional outcome., Results: In univariate analysis, an increase in either the oGS or mGS was associated with a higher risk for hospital mortality, development of CHC, and poor early functional outcome. The correlation of the oGS and mGS was excellent using Pearson's product-moment (r = 0.918; p < 0.001). The predictive value of the oGS was superior to the predictive value of the mGS using receiver operating characteristics and corresponding area under the curve value as there was no statistical significant differences between the scores., Conclusions: Our study confirms the validity of the recently introduced mGS to quantify the volume of IVH and extends its value in aSAH. However, the mGS offers no additional predictive value for hospital mortality, development of CHC, and poor early functional outcome in patients with aSAH patients compared to the less complex oGS.

Background: The aim of this study was to evaluate serum nimodipine concentrations in patients with aneurysmal subarachnoid hemorrhage (SAH) after parenteral therapy and a following course of enteral administration., Methods: SAH patients were treated with intravenous nimodipine (2 mg/h) during the 1st week after hemorrhage, and on day 8, we switched over to enteral administration (60 mg/4 h), either orally or by gavage. Serum nimodipine concentrations were measured on days 3, 5, 8, 9 and 12. Area under the curve (AUC) was calculated during parenteral and enteral therapy. The data of 15 patients were analyzed retrospectively., Results: In this study, 157 blood samples were obtained. In seven samples, during the administration by gavage to two patients with high-grade SAH, the serum nimodipine concentrations were negligible. The AUC values during parenteral administration (median 149.3 ng-h/ml) were significantly higher than during oral administration on days 9 (median 92.1 ng-h/ml) and 12 (median 44.1 ng-h/ml) in seven patients (p = 0.030 and p = 0.016, respectively). The AUC values during parenteral administration were significantly higher than during administration by gavage on day 9 in eight patients (median 87.9 and 34 ng-h/ml, respectively, p = 0.001). The AUC values during enteral administration were higher in patients who received nimodine orally than in those who received it by gavage (median 52.3 and 23.1 ng-h/ml, respectively, p = 0.006)., Conclusions: Enteral administration of nimodipine showed lower bioavailability during the 2nd week after SAH compared to parenteral application during the 1st week. Negligible serum concentrations were even expected when nimodipine was given by gavage in patients with high-grade SAH, thus suggesting that parenteral administration may be the better route in these patients.

Background: Reliable prognostic tools to estimate the case fatality rate (CFR) and the development of chronic hydrocephalus (CHC) in aneurysmal subarachnoid hemorrhage (SAH) are not well defined. This study aims to investigate the practicability and reliability of Fisher, Graeb, and LeRoux scores for SAH patient prognosis., Methods: A total of 206 patients with aneurysmal SAH were retrospectively analyzed in prediction of CFR and CHC. Clinical data was evaluated and grading was performed using Fisher, Graeb, and LeRoux scores. Univariate and multivariate analyses were performed to identify relevant predictive parameters., Results: CFR was 17.0 % and was associated with higher age, higher Hunt & Hess (H&H) grade, lower Glasgow Coma Scale (GCS) at admission, as well as a higher Fisher, Graeb, and LeRoux score (p < 0.001). There were 19.9 % that developed CHC requiring permanent cerebrospinal fluid diversion. Low initial GCS (p = 0.003), high H&H (p < 0.001), intracerebral hematoma (p = 0.003), high Fisher (p = 0.047), Graeb and LeRoux scores (p < 0.001) were associated with a higher rate of ventricular-peritoneal shunting (VPS) in surviving patients. In multivariate analyses, Graeb score (odds ratio (OR) 1.183 [1.027, 1.363], p = 0.020), LeRoux score (OR 1.120 [1.013-1.239, p = 0.027), and H&H (OR 2.715 [1.496, 4.927], p = 0.001) remained independent prognostic factors for VPS., Conclusions: Graeb or LeRoux scores improve the prediction of shunt dependency and in parts of CFR in aneurysmal SAH patients therefore confirming the relevance of the extent and distribution of intraventricular blood for the clinical course in SAH.

Background: Vaccination against tumour-associated antigens is one approach to elicit anti-tumour responses. We investigated the effect of polynucleotide (DNA) vaccination using a model antigen (E. coli lacZ) in a syngeneic gliosarcoma model (9L)., Methods: Fisher 344 rats were vaccinated thrice by intramuscular injection of a lacZ-encoding or a control plasmid in weekly intervals. One week after the last vaccination, lacZ-expressing 9L cells were implanted into the striatum., Results: After 3 weeks, in lacZ-vaccinated animals the tumours were significantly smaller than in control-vaccinated animals. In cytotoxic T cell assays lysis rates of >50 % could only be observed in a few of the lacZ-vaccinated animals. This response was directed against lacZ-expressing and parental 9L cells but not against syngeneic MADB 106 adenocarcinoma cells. In Elispot assays interferon-γ production was observed upon stimulation with 9LlacZ and 9L wild-type but not MADB 106 cells. This response was higher for lacZ-immunized animals. All animals revealed dense infiltrates with CD8+ lymphocytes and, to a lesser extent, with NK cells. CD25-staining indicated cells possibly associated with the maintenance of peripheral tolerance to self-antigens. All tumours were densely infiltrated by microglia consisting mostly of ramified cells. Only focal accumulation of macrophage-like cells expressing ED1, a marker for phagocytic activity, was observed., Conclusion: Prophylactic DNA vaccination resulted in effective but incomplete suppression of brain tumour formation. Mechanisms other than cytotoxic T cell responses as measured in the generally used in vitro assays appear to play a role in tumour suppression.

Background: This article discusses data from 3 randomized phase 3 trials, supporting a role for surgery in glioblastoma., Methods: Data were reviewed by extent of resection during primary surgery from the ALA-Glioma Study (fluorescence-guided versus conventional resection), the BCNU wafer study (BCNU wafer versus placebo), and the EORTC Study 26981-22981 (radiotherapy versus chemoradiotherapy with temozolomide)., Results: For glioblastoma patients in the ALA study, median survival was 16.7 and 11.8 months for complete versus partial resection, respectively (P < 0.0001). Survival effects were maintained after correction for differences in age and tumor location. For glioblastoma patients who received ≥90% resection in the BCNU wafer study, median survival increased for BCNU wafer versus placebo (14.5 versus 12.4 months, respectively; P = 0.02), but no survival increase was found for <90% resection (11.7 versus 10.6 months, respectively; P = 0.98). In the EORTC study, absolute median gain in survival with chemoradiotherapy versus radiotherapy was greatest for complete resections (+4.1 months; P = 0.0001), compared with partial resections (+1.8 months; P = 0.0001), or biopsies (+1.5 months; P = 0.088), suggesting surgery enhanced adjuvant treatment., Conclusion: Complete resection appears to improve survival and may increase the efficacy of adjunct/adjuvant therapies. If safely achievable, complete resection should be the surgical goal for glioblastoma.

Objective: Adjuvant systemic chemotherapy increases survival of primary malignant glioma patients beyond 12-18 months. The only interstitial chemotherapy treatment approved for malignant glioma is Gliadel wafer containing carmustine (BCNU) placed in the resection cavity at surgery. Analysis of a large trial by Westphal and colleagues (n = 240) showed a 29% risk reduction (P = 0.03) in the BCNU wafer-treated group over the course of the 30-month trial. Long-term follow-up of these patients was undertaken to determine the survival benefit at 2 and 3 years., Methods: Survival proportions for the placebo and treatment groups over the 56-month study were estimated by the Kaplan-Meier method. Multiple-regression analyses using the Cox proportional hazards model included prognostic factors of age, KPS, and tumor type. A secondary analysis was conducted for 207 GBM patients., Results: Of the 59 patients available for long-term follow-up, 11 were alive at 56 months: 9 had received BCNU wafers and 2 had received placebo wafers. Median survival of patients treated with BCNU wafers was 13.8 months vs 11.6 months in placebo-treated patients (P = 0.017) with a hazard ratio of 0.73 (P = 0.018), representing a 27% significant risk reduction. This survival advantage was maintained at 1, 2, and 3 years and was statistically significant (P = 0.01) at 3 years. Two of 207 GBM patients remained alive at the end of the follow-up period, both in the BCNU wafer-treated group., Conclusion: Malignant glioma patients treated with BCNU wafers at the time of initial surgery in combination with radiation therapy demonstrated a survival advantage at 2 and 3 years follow-up compared with placebo.